2014 09 PDF

®
September 2014 Volume 29 Number 9 www.spectroscopyonline.com
Trace Elemental
Analysis and
Wine Chemistry
Headspace Raman
Spectroscopy
Good Documentation
Practices in
Pharmaceutical Labs
Calibration and Units of
Measure in Spectroscopy
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CONTENTS 

  

COLUMNS
September 2014
Volume 29 Number 9 Molecular Spectroscopy Workbench . . . . . . . . . . . . . . 14
Headspace Raman Spectroscopy
We examine vapor-phase Raman spectroscopy through the acquisition of spectra from gas
molecules confined to the headspace.
David Tuschel
Focus on Quality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
What Do You Mean by Good Documentation Practices?
A closer look at the U.S. Pharmacopeial Convention’s (USP) draft general chapter <1029> on
good documentation practices.
R.D. McDowall
Chemometrics in Spectroscopy . . . . . . . . . . . . . . . . . 26
Units of Measure in Spectroscopy, Part II: What Does It Mean?
Now that we have shown the relationships between different units for concentration, we
continue by demonstrating their effects on the data we collected and used for our examples.
What are the ramifications and consequences of these findings?
Howard Mark and Jerome Workman, Jr.
Cover image courtesy of

Getty Images. Spectroscopy Spotlight . . . . . . . . . . . . . . . . . . . . . . 32
Improving Drug Formulation with Raman and IR Spectroscopy
Lynne Taylor of the Department of Industrial and Physical Pharmacy at Purdue University
discusses her research using Raman and IR spectroscopy to study drugs and drug excipients
as well as her research with crystallization and studying the physicochemical properties of
drug-rich nanodroplets.
ON THE WEB
WEB SEMINARS
PEER-REVIEWED ARTICLES
Dual View ICP-OES Minus the Wait: How Trace Elemental Analysis Provides
Find Out How the Agilent 5100 ICP-
OES Corrects the Vision of Dual View
Important Insight into Wine Chemistry . . . . . . . . . . . . . . . . . . . . . . . 34
Ross Ashdown Bahten, Agilent Technologies Examples are shown that highlight how elemental fingerprinting could provide valuable
information about the geographical origin of a food or beverage as well as how different
Nanoscale IR Spectroscopy in steps in the production of wines impact their elemental composition.
Materials and Life Sciences
Curt Marcott, Light Light Solutions; Craig Helene Hopfer, Jenny Nelson, Thomas S. Collins, Hildegarde Heymann, and Susan E. Ebeler
Prater and Kevin Kjoller, Anasys Instruments
Learn the Tricks of the Trade to
Prepare Your Lab for USP Chapters
<232> and <233> Sulfobutyl Ether-β-Cyclodextrin–Assisted Fluorescence
Daniel Kutscher and Sanja Asendorf,
Thermo Fisher Scientific
Spectroscopy for Determination of L-Amlodipine in Tablets . . . . . . . . . . . . 40
This study describes a validated spectrofluorometric method for the analysis of L-amlodipine
Exploding Common Myths About
Modular Spectroscopy
in tablets.
Yvette Mattley, Ocean Optics Lin Yang, Jiaqi Xie, Xiaoming Deng, Shenzhi Lai, and Xiaoming Chen
Interest of High Resolution ICP-OES
for Rare Earth Elements Analysis in
Various Applications, From Geology
to Permanent Magnets
Alice Stankova, Horiba Scientific
DEPARTMENTS
spectroscopyonline.com/WebSeminar
News Spectrum. . . . . . 12 Products & Resources. 46 Ad Index . . . . . . . . . . . . 50

Like Spectroscopy on Facebook:
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Editorial Advisory Board

Fran Adar Horiba Scientific R.D. McDowall McDowall Consulting
Ramon M. Barnes University of Massachusetts Gary McGeorge Bristol-Myers Squibb
Linda Baine McGown Rensselaer Polytechnic Institute

Matthieu Baudelet University of Central Florida
Robert G. Messerschmidt Rare Light, Inc.
Paul N. Bourassa Blue Moon Inc.
Francis M. Mirabella Jr. Mirabella Practical Consulting
Michael S. Bradley Thermo Fisher Scientific Solutions, Inc.
Deborah Bradshaw Consultant John Monti Montgomery College
Ashok L. Cholli Polnox Corporation Michael L. Myrick University of South Carolina
John W. Olesik The Ohio State University

David Lankin University of Illinois at Chicago,
College of Pharmacy Jim Rydzak GlaxoSmithKline
Barbara S. Larsen DuPont Central Research Jerome Workman Jr. Unity Scientific
and Development
Spectroscopy’s Editorial Advisory Board is a group of distinguished individuals

Ian R. Lewis Kaiser Optical Systems assembled to help the publication fulfill its editorial mission to promote the effec-
tive use of spectroscopic technology as a practical research and measurement tool.
With recognized expertise in a wide range of technique and application areas, board
Rachael R. Ogorzalek Loo University of California Los Angeles, members perform a range of functions, such as reviewing manuscripts, suggesting
David Geffen School of Medicine authors and topics for coverage, and providing the editor with general direction and
feedback. We are indebted to these scientists for their contributions to the publica-
tion and to the spectroscopy community as a whole.
Howard Mark Mark Electronics

2015
SPRING MEETING & EXHIBIT
April 6–10, 2015 | San Francisco, California
CALL FOR PAPERS

Abstract Submission Opens September 23, 2014
Abstract Submission Deadline October 23, 2014
www.mrs.org/spring2015 
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News Spectrum
Talk on Raman Studies of the Tyrolean The awards are given solely on merit, and the number
Iceman a Highlight of Upcoming presented each year is not preset.
Confocal Raman Imaging Symposium Spectro Scientific Wins Innovation Research
The 11th Confocal Raman Imaging Symposium, hosted by Award for Work with U.S. Armed Forces
WITec, will include a talk by Albert Zink from the EURAC-
Spectro Scientific (Chelmsford, Massachusetts), a developer
Institute for Mummies and the Iceman about Raman
and manufacturer of analytical tools and software for fluid
investigations of the Tyrolean Iceman. The symposium,
and machine condition monitoring, has earned a Small
taking place September 29–October 1 in Ulm, Germany,
Business Innovation Research (SBIR) Phase II award of
will cover various aspects of modern Raman microscopy,
$750,000 for its work in reevaluating the Joint Oil Analysis
and provide insights into confocal Raman imaging and its
Program (JOAP), which consolidates and coordinates the oil
applications.
analysis programs of the U.S. Army, Navy, and Air Force. The
Other symposium speakers include experts in Raman
U.S. Small Business Administration SBIR award promotes
spectroscopy from academia and industry. The talks will
high-tech innovation in the fulfillment of specific research
highlight a range of Raman spectroscopy applications in
and development needs. The contract awarded to Spectro
life science, nanotechnology, materials science, graphene
Scientific for Phase II extends into 2016.
research, and climate research.
Spectro undertook the reevaluation effort to improve the
Technical talks about the general principles of the technique,
JOAP by modifying processes and equipment to create
microscope configurations, and resolution will also be
more effective oil analysis. The JOAP was formed following
featured at the symposium. Further conference highlights
the mid-1950s U.S. Bureau of Naval Weapons research
include contributed talks and a poster session (to which
into oil analysis as a tool to indicate and predict machine
all attendees are invited to submit their abstracts), the
component wear. ◾
conference dinner with the best poster
award ceremony, and a demonstration
of WITec’s new RISE Microscope
IS THERE AN APP FOR THAT?

for correlative Raman imaging and
scanning electron microscopy.
Renishaw Wins Queen’s

HIGHLIGHTS OF APPS FOR SPECTROSCOPY
Award for Enterprise:
Innovation 2014 4G 100% 11:59 AM
Renishaw (Hoffman Estates, Illinois),
a global engineering technologies APP NAME: Fluorescence Spectra Analyzer
company, has received the Queen’s OFFERED BY: BioLegend Inc.
Award for Enterprise 2014 in the
PLATFORMS: Android
Innovations category for its inVia Raman
microscope. The award was granted WHAT IT DOES: BioLegend’s Fluorescence Spectra
for the continuous development of Analyzer is designed for the analysis of excitation and
the inVia, which enables the rapid emission spectra of commonly used fluorochromes for
generation of high-definition two- and flow cytometry. According to the company, the app al-
lows users to add custom filters, use common laser lines,
three-dimensional chemical images for
and zoom in and out. It reportedly contains a variety of
material analysis.
excitation and emission spectra.
The inVia microscope can be used in
chemical analysis; materials science;
pharmaceutical analysis; semiconductor
research; forensics; gemology;
antiquities analysis; and green energy
development, such as photovoltaics.
The Queen’s Awards for Enterprise
are given out each year by the
Queen of England on the advice of
the British Prime Minister, who is
assisted by an advisory committee
that includes representatives
of government, industry and
commerce, and trade unions.
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© 2014 PerkinElmer, Inc. 400298_03. All trademarks or registered trademarks are the property of PerkinElmer, Inc. and/or its subsidiaries.
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Molecular Spectroscopy Workbench

Headspace Raman Spectroscopy
We examine vapor-phase Raman spectroscopy through the acquisition of spectra from gas mol-
ecules confined to the headspace of sealed containers. Studying the Raman spectra of the liquid and
vapor phases of compounds with different functional groups, degrees of hydrogen bonding, and
polarity provides insight into the energetics of molecular interactions.
David Tuschel
Y ou were probably first introduced to rotational

and vibrational-rotational spectroscopy as an
undergraduate. Perhaps you even applied what
you were learning in the lecture hall and from text
books in a physical chemistry laboratory involving
functional groups. We also explore the phenomenon of
Fermi resonance and discuss the effect of spin statistics
on high spectral resolution vibrational-rotational di-
atomic molecules.
infrared absorption spectroscopy of gases. If so, that Carbonated Beverages

may well have been your last encounter with vibra- Carbonated beverages such as soda, beer, or sparkling
tional spectroscopy of compounds in the vapor phase. water have a substantial amount of CO 2 dissolved
Those of us who perform Raman spectroscopy do in them, which provides the fizz when first opening
so almost entirely with materials in the condensed the bottle or can and the tingle when drinking the
phase; that is, liquids or solids. However, many of the contents. We’ve all experienced drinking a soft drink
compounds with which we work have some measure that has lost most of its CO 2 ; we say the drink has
of volatility, particularly liquids that evaporate quite gone f lat. Our own experience with beverages that
rapidly, such as methanol, isopropyl alcohol, and ac- have gone f lat teaches us that CO 2 is not particularly
etone. Consequently, sealed containers of compounds, soluble in water at atmospheric pressure and, for that
solutions, or mixtures will have some number of reason, carbonated beverages must be securely sealed.
volatilized molecules in the headspace between the Consequently, carbonated beverages have a high par-
condensed phase and the container seal. A transpar- tial pressure of CO 2 in the headspace.
ent container offers Raman spectroscopists the ability One such carbonated beverage is beer. Fluorescence
to probe both the condensed and vapor phase in the overwhelms the Raman scattering from the liquid
headspace above the sample. portion of the sealed beer sample when using 532-nm
In this installment, we examine vapor-phase Raman excitation (the excitation wavelength for all spectra
spectroscopy through the acquisition of spectra from shown in this article). However, guiding the laser
gas molecules confined to the headspace. Compari- beam above the liquid through the headspace yields
sons of the vapor-phase and condensed-phase spectra the spectrum of CO 2 shown in Figure 1. One of the
reveal the significant effects of molecular interactions, most striking features of Raman spectra from the
particularly hydrogen bonding, on the vibrational spec- vapor phase are how narrow the bands are relative to
trum. The degree to which certain Raman bands differ those obtained in the liquid phase. The full width at
in energy and bandwidth (primarily from collisional half maximum (FWHM) of the CO 2 bands is 0.9 cm -1!
broadening) between the vapor and condensed phases The spectrum consists of six bands: one attributed to
provides insight into the variation of molecular interac- O 2 and the remaining five bands attributed to CO 2 .
tions of compounds of different molecular structure and This may seem a little strange given that group theory
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w w w. s p e c t r o s c o p y o n l i n e . c o m September 2014 Spectroscopy 29(9) 15
predicts only one Raman active is so great that isotopic (13 C16 O 2) spectrum of sparkling water is
mode for CO 2 , the ν1 symmetric and excited state or so-called hot nearly identical to that from beer.
stretching mode. (ν11 and 2ν21) bands appear in the Now, without the overwhelming
A phenomenon called Fermi Raman spectrum. f luorescence generated by the liq-
resonance accounts for the ap- The Raman spectra obtained uid beer, the Raman spectrum of
pearance of multiple CO 2 Raman from sparkling water offer us an the CO 2 in liquid sparkling water
bands. The symmetric stretching opportunity to compare the spec- can be obtained. The liquid spec-
mode of CO 2 is of Σ+ g symmetry trum of CO 2 in the vapor phase trum consists of bands at 1272.7
and is expected at approximately with that dissolved in water. and 1379.6 cm -1 (CO 2) and 1633.6
1330 cm -1 (1). The ν2 doubly de- Raman spectra of CO 2 and O 2 from cm -1 (the bending mode of H 2 O).
generate bending mode is Raman the headspace of sparkling water The effect of the solvent (H 2 O)
forbidden, but does appear in the and the liquid itself are shown in on the solute (CO 2) can be seen
infrared absorption spectrum at Figure 2. The headspace Raman in the positions and widths of the
667 cm -1 (2). However, the over-
tone (2ν2) has Σ+ g symmetry and is
expected at 1334 cm -1. So, we have
a fundamental vibrational mode
and an overtone of approximately Get the big picture with THz-Raman®
equal energies and the same sym-
metry. Therefore, these two energy Structural Fingerprint Chemical Fingerprint
± 5 cm-1 to 200 cm-1 200 cm-1 to 2,000 cm-1
states can interact, and this inter-
action is called Fermi resonance.
This type of resonance can pro-
duce quite striking effects with
Polymorphs are clearly
respect to both Raman scattering distinguished by strong, low
strength and perturbation of the frequency/THz-Raman signals
vibrational states — that is, Raman
band positions.
The assignments of the beer
headspace CO 2 Raman bands are
shown in Table I in accordance
with the assignments of Hanf and
coworkers (3). The very strong Both Stokes and anti-Stokes signals Complete chemical
from ± 5cm-1 to 200cm-1 fngerprint
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been assigned to ν1 and 2ν2 , re-
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we see a difference of 103 cm -1.
In addition to the band splitting,
one also observes a so-called bor-
rowing of intensity with Fermi
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Table I: Assignment of Raman bands in

beer headspace spectrum of Figure 1
Molecular Raman Band
1387.5 Symbol
Headspace Formula (cm–1)
1500 ν11/ν1 12C16O /13C16O 1264.4
Intensity (counts)
2 2
1284.8 FWHM: 0.9 cm–1 ν1 12C16O 1284.8
2
2ν2 13C16O 1369.3

2
1000
2ν2 12C16O 1387.5
2
2ν21 12C16O 1408.8

2
1369.3
500
1408.8 O2
1264.4 CO 2 ν1 and 2ν2 bands. The shifts
between the vapor phase and the
1200 1250 1300 1350 1400 1450 1500 1550 1600 water solubilized CO 2 ν1 and 2ν2
Raman shift (cm ) –1 bands are -12.3 and -8.1 cm -1, re-
spectively. Given that the shift in
Figure 1: Raman spectrum of CO2 and O2 from the headspace of beer. the ν1 band is 50% greater than
that observed for the 2ν2 band, it
is not surprising that the intensity
of the solubilized CO 2 ν1 band is
significantly more diminished.
1387.7 Also, the FWHM of the 2ν2 bands
Intensity (arbitrary units)
1285.0 FWHM: 0.9 cm–1 in the vapor phase and water solu-
bilized CO 2 are 0.9 and 9.9 cm -1,
Headspace respectively. The band width of the
O2 solvated CO 2 is 10 times greater
than that in the vapor phase,
1633.6 thereby indicating the strength of
1379.6 the interactions of CO 2 with the
1272.7 Liquid
water solvent. The Raman spectra
of the headspace and solvated CO 2
demonstrate that Raman spectros-
1200 1300 1400 1500 1600 1700 1800 1900 copy is well suited for the study of
Raman shift (cm–1) molecular interactions of solute
and solvent.
Figure 2: Raman spectra of CO2 and O2 from the headspace of sparkling water and the liquid.
Effect of Hydrogen Bonding
on the Vibrational Spectrum
In the previous section, we com-
pared the spectra of a gas in the
vapor phase and solubilized by
3340 water. Here, we compare the spec-
N-H
tra of compounds in the liquid and
Headspace 3659 vapor phases and see the effect of
O-H
hydrogen bonding manifest in the
vibrational spectrum of the liquid.
Our first example consists of house-
Liquid hold ammonia purchased at the gro-
cery store. In this case, our head-
3314 3424
space Raman spectrum consists of
N-H O-H both the solute (NH 3) and solvent
(H 2O). The Raman spectra of the
2800 3000 3200 3400 3600 3800 liquid and headspace of household
Raman shift (cm–1) ammonia are shown in Figure 3.
The spectrum of the liquid consists
Figure 3: Raman spectra of liquid- and vapor-phase household ammonia.
of a very broad band ranging from
approximately 3000 cm-1 to
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3700 cm-1 and consisting of two a substantially lesser degree. The functional groups can be expected
partially resolved broad peaks. 2832 and 2941 cm-1 bands shift to to exhibit hydrogen bonding and
This is the Raman scattering due 2846 and 2956 cm-1, a shift of 14 have strong molecular interactions.
to water and the enormous band- and 15 cm-1, respectively. However, as the nonpolar portion
width is attributed to hydrogen These differences in Raman of the molecule becomes larger
bonding. The much narrower peak band positions between the liquid or the polar functional group is
protruding at 3314 cm-1 is the ν1 and vapor phases provide insight removed, we can expect the ener-
symmetric stretch of NH 3. The into the energetics of the molecu- getics of molecular interaction to
Raman bandwidths clearly indicate lar interactions in the liquid phase. diminish. Compounds of medium
that the strength of hydrogen bond- Of course, hydrogen bonding of- polarity or entirely nonpolar can
ing among water molecules is far fers the strongest type of molecu- be expected to have smaller differ-
greater than that with ammonia lar interaction that we can expect ences between the Raman spectra
molecules. to see, and compounds bearing OH of the liquid and vapor phases.
In fact, the effects of hydrogen
bonding are made stunningly clear
when one compares the liquid
spectrum to that of the headspace.
The NH 3 symmetric stretch in the
vapor phase is much narrower and
PIONEERS
is shifted relative to the solvated
species by 26 cm -1. The absence of
solvation by the water molecules
reduces the molecular interac-
tions and collisional broadening
and thereby causes the NH 3 sym-
metric stretching mode to shift
to higher energy and narrows the
distribution of vibrational states.
Hydrogen bonding is even more
significant in the liquid phase of The Bathyscaph Trieste arrived at the Earth’s most
water, so the difference between extreme depth on 23. January 1960.
OH stretching bands from water in
the liquid and vapor phases is even
more dramatic. Without the con-
tribution from hydrogen bonding, 5 µm
the OH stretching bands narrow

significantly and shift to 3659 cm -1
where a single asymmetric band
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before with WITec’s pioneering technology.
shown in Figure 4. Raman scatter-
ing from the CH stretching vibra-
tional modes appear at energies less
than 3000 cm-1. The OH stretch of
methanol appears as a broad band
centered at 3340 cm-1 in the liquid
phase; however, it splits into two
partially resolved bands at 3684 alpha300 R alpha500 AR alpha300 SR alpha300 AR+
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ing modes are also affected, but to
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Analyze 2846

2956
Everything...
3684, 3697
Headspace O-H
2832 2941
Liquid
3340
O-H
2600 2800 3000 3200 3400 3600 3800

Raman shift (cm–1)
Figure 4: Raman spectra of liquid- and vapor-phase methanol.
N2 2952.8

2262.9 Headspace FWHM: 3.5 cm–1
2940.2
2249.6
Liquid FWHM: 7.6 cm–1
2000 2200 2400 2600 2800 3000 3200

-
Sample solids, liquids, polymers
Figure 5: Raman spectra of liquid- and vapor-phase acetonitrile.
- -
Diamond, ZnSe or Ge crystals
- spectral data -
to optimize
Organic Compounds with
Different Strengths of Molecular Interactions
- Acetonitrile is considered a medium polarity solvent
that is miscible with many organic solvents (except
Add options as your saturated hydrocarbons) and water. For the pur-
sampling needs change poses of our discussion, we can think of it as having
replaced the OH group on methanol with the CN
nitrile group. Therefore, we might expect that the
Save time and improve differences between the liquid- and vapor-phase CH 3
- - - stretches of acetonitrile might be comparable to those
your analysis quality
of methanol. However, that expectation is not met in
the Raman spectra of the liquid and vapor phase of
acetonitrile shown in Figure 5.
...with PIKE MIRacle - TM
The Raman spectrum of the liquid phase features
The Most Universal ATR two strong bands at 2249.6 and 2940.2 cm -1 attributed
to the CN stretch and CH 3 stretch, respectively. Note
that the CH 3 stretch bandwidths of both liquid- and
vapor-phase acetonitrile are significantly narrower
than those observed in either liquid- or vapor-phase
methanol spectra. In fact, the acetonitrile CH 3 stretch
www.piketech.com has a FWHM of only 7.6 cm -1 in the liquid phase and
tel: 608-274-2721 is reduced by approximately 50% to 3.5 cm -1 in the
vapor phase. As expected, the CN stretch and CH 3
stretch bands shift to higher energy in the vapor
phase, 2262.9 and 2952.8 cm -1. It is noteworthy that
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992.1
PIKE
FWHM: 1.1 cm–1
MIRacle
993.4
Headspace TM
984.2
991.4
FWHM: 2.1 cm–1 Liquid
982.9
960 980 1000 1020 1040

Figure 6: Raman spectra of liquid- and vapor-phase benzene.
1556.4
O2
400
Intensity (counts)
300
Q
200
O S
100
1350 1400 1450 1500 1550 1600 1650 1700 1750
Figure 7: Raman spectrum of oxygen in air. Note the rotational side -

bands to the symmetric stretch at 1556.4 cm-1.
The PIKE MIRacle is- a universal
TM - sampling
the phase-related energy shifts are 13.3 and 12.6 cm -1 accessory for analysis of solids, liquids, pastes,
- -
for the CN and CH stretches, respectively. Those gels and intractable materials. It is a single
shifts are approximately equal and slightly less than -
the 14–15 cm -1 difference that we observed for the CH reflection ATR with highest IR throughput
stretching in methanol. Comparing all of these spec- making it ideal for sample identification and
tral features and their differences in the acetonitrile
and methanol spectra, we can infer that the molecular
QA/QC applications. Advanced options include
interactions of methanol are greater than those of three reflection ATR crystal plates to optimize
acetonitrile.
Our comparison of the Raman spectra of liquid and - lower concentration
for - -components. Easily
vapor phases now progresses to the nonpolar solvent change crystal plates to analyze a broad
benzene. We expected the molecular interactions to
be weak compared to those of polar and medium po-
spectrum of sample types.
larity solvents. The Raman spectra of benzene in the
liquid and vapor phase shown in Figure 6 confirm
-
that expectation. Here, we focus our attention on the
FTIR sampling made easier
ring breathing mode, which appears at 991.4 cm -1
with a FWHM of 2.1 cm -1 in the liquid spectrum. The
Raman band assigned to the ring breathing mode of
benzene in the liquid phase is actually narrower than
any of the bands from either methanol or acetonitrile PIKE Technologies
in the vapor phase. This is a measure of just how weak www.piketech.com
the molecular interactions are. Nevertheless, the va- tel: 608-274-2721
por-phase spectrum reveals a shift of the ring breath-
ing mode band of +0.7 cm -1 to 992.1 cm -1 and a nar-
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rowing of the FWHM to 1.1 cm -1.

So that even when the molecular
130
interactions in the liquid phase are
Q weak, it is clear that in the vapor
120 O2 phase they are still weaker.
Intensity (counts)
O S Studying the Raman spectra

of the liquid and vapor phases of
110
compounds with different func-
tional groups, degrees of hydrogen
100 bonding, and polarity provides
insight into the energetics of mo-
lecular interactions.
90
Vibrational-Rotational
1350 1400 1450 1500 1550 1600 1650 1700 1750 Raman Spectra of
Raman shift (cm–1) Atmospheric Molecules
We now move from compounds
Figure 8: Raman spectrum of oxygen in air featuring the rotational side bands. The FWHM of the that are liquid at room tempera-
rotational side bands are 1.01 cm-1. ture to atmospheric diatomic mol-
ecules. The primary components
of air are N2 and O 2 . Therefore,
we can expect to find a contribu-
2330.0 tion from these molecules in most
N2 headspace Raman spectra. Having
1000 Q no dipole moment, these molecules
are of course infrared inactive.
However, because the polarizabili-
ties of these molecules are aniso-
500 tropic, one can observe Raman ac-
tive rotational transitions in both
the rotational and vibrational-
O S rotational spectra. A discussion of
the fundamental molecular physics
2150 2200 2250 2300 2350 2400 2450 2500 and nuclear spin statistics of rota-
Raman shift (cm ) –1 tional and vibrational-rotational
Raman spectroscopy is beyond the
Figure 9: Raman spectrum of nitrogen in air. Note the rotational side bands to the symmetric scope of this installment. Never-
stretch at 2330.0 cm-1. theless, you will need to know just
a few facts about the quantum me-
chanics of vibrational-rotational
110 Raman spectroscopy to appreciate
Q what you observe in the spectra of
N2 N2 and O 2 .
Intensity (counts)
100
The selection rules for the vibra-
o s tional-rotational Raman spectrum
90 of a diatomic molecule are given by
80 O Branch: ν vib – ν rot , Δ J = -2 [1]
Q Branch: ν vib , Δ J = 0 [2]

70
S Branch: ν vib + ν rot , Δ J = +2 [3]
2150 2200 2250 2300 2350 2400 2450 2500
Raman shift (cm–1) where J is the rotational quantum
number. Note that the Raman
Figure 10: Raman spectrum of nitrogen in air featuring the rotational side bands. The FWHM of selection rules differ from the ro-
the rotational side bands are 0.77 cm-1. tational infrared active absorption
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selection rule of Δ J = ±1. An additional consideration interactions. Finally, vibrational-rotational Raman

is that the rotational wavefunction must have parity spectroscopy was demonstrated with the atmospheric
such that the overall wavefunction is symmetric. A components of N2 and O 2 .
consequence of these rules is that for O 2 with a total
spin of 0, the rotational lines originating from a J References
state with an even number will be missing. In con- (1) C.N. Banwell, Fundamentals of Molecular Spectroscopy, 3rd
trast, N2 has a total spin of 1 and the rotational lines ed. (McGraw-Hill, London, 1983), p. 96.
originating from all J states will be Raman active. We (2) L.A. Woodward, Introduction to the Theory of Molecular
simply state here without detailed explanation that Vibrations and Vibrational Spectroscopy (Oxford, London,
nuclear spin statistics dictate that for N2 , which has a 1972), p. 348.
total spin of 1, the intensity ratio of alternate lines is (3) S. Hanf, R. Keiner, D. Yan, J. Popp, and T. Frosch, Anal. Chem.
2:1, whereas O 2 with a total spin of 0 has an intensity 86, 5278–5285 (2014).
ratio of 1:0.
Now we are prepared to understand the vibra-
tional-rotational Raman spectra of these atmo- David Tuschel is a Raman applications
spheric diatomic gases that are likely to be ob- manager at Horiba Scientific, in Edison, New
served in any Raman headspace measurement. The Jersey, where he works with Fran Adar. David
vibrational-rotational Raman spectrum of O 2 in air is sharing authorship of this column with
is shown in Figure 7. The spectrum consists of the Fran. He can be reached at: david.tuschel@
main vibrational symmetric stretch or Q branch at horiba.com.
1556.4 cm -1. The O and S rotational branches can
be seen on the low and high energy sides of the Q
branch, respectively. Changing the intensity scale of
Figure 7, we now have an expanded view of the ro- For more information on this topic, please visit:
tational side bands as seen in Figure 8. The narrow www.spectroscopyonline.com
peaks on either side of the Q branch correspond to
the vibrational-rotational Raman selection transi-
tions described in the equations above. The side
bands of O 2 are all separated by two J states, origi-
nate from odd valued J states, and the intensities are
all evenly distributed proportional to the popula-
tions of the original states. Note how narrow the O 2
sidebands are with a FWHM of 1.01 cm -1.
The vibrational-rotational Raman spectrum of N2
in air is shown in Figure 9. The Q branch of N2 is sig- Optimize the precision of your
nificantly stronger than that of O 2 , primarily because measurements and the performance
its concentration in the atmosphere is significantly of your instruments
higher than that of O 2 . Note also that the O and S
Check out our convenient
rotational sidebands are significantly weaker than
& informative new website
those of O 2 . Nevertheless, expansion of the intensity
scale as seen in Figure 10 reveals the alternating 2:1 W W W. SPEC T R A L-S YSTEMS.COM
intensity of the sidebands as predicted by nuclear spin

Request our
statistics. The side bands are all separated by one J
new catalog free
state, originate from even and odd valued J states, and or download a PDF
the intensities are all evenly distributed proportional immediately from
to the populations of the original states and with re- our website!
spect to nuclear spin statistics. The O and S rotational
sidebands of N2 with a FWHM of 0.77 cm -1 are even
narrower than those of O 2 .
Conclusions
We presented vapor-phase Raman spectra of dissolved
gases that exhibit Fermi resonance. The liquid- and
vapor-phase Raman spectra of nonpolar, medium S U P P LY I N G T H E M O S T CO M P R E H E N S I V E L I S T O F
polarity, and polar solvents were analyzed and the INFR ARED OP T IC AL COMPONENTS FOR OV ER 30 Y E ARS
differences demonstrated that Raman spectroscopy PHONE: 8 4 5.8 9 6.220 0 • INFO @SPEC TR A L- SYS TEMS.COM
is well suited for studying the energetics of molecular
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Focus on Quality
What Do You Mean by Good
Documentation Practices?
The U.S. Pharmacopeial Convention (USP) has issued a draft general chapter
<1029> on good documentation practices for comment. What can we learn from
this draft?
R.D. McDowall
I n the May 2014 issue of Pharmacopeial Forum, the U.S.

Pharmacopeial Convention (USP) issued a draft general
chapter on good documentation practices (GDP) (1).
Note that this GDP must not be confused with the GDP in
the European Union (EU) “good manufacturing practice”
as follows: “There are two primary types of documentation
used to manage and record GMP compliance: instructions
(directions, requirements) and records/reports” (2). As
shown in Figure 1, the execution of an instruction results in
the generation of a record, records, or a report. It is the exis-
(GMP), which stands for good distribution practice in that tence of accurate and reliable records that demonstrate that
context. When GDP is used in this column, the “D” will instructions have been followed and, therefore, compliance
mean documentation. with GMP regulations.
Chapter 4 (2) goes into more detail about records and
EU GMP Chapter 4 on Documentation reports:
Before starting to review the United States Pharmacopeia • Records: Provide evidence of various actions taken to
(USP) draft general chapter, let us look at what exists in demonstrate compliance with instructions — for example,
the regulated world as documentation is the key to compli- activities, events, investigations, and, in the case of manu-
ance with either good laboratory practice (GLP) or GMP factured batches, a history of each batch of product, in-
regulations. As the section titled “Principle” in EU GMP cluding its distribution. Records include the raw data that
chapter 4 on documentation states in the first sentence, is used to generate other records. For electronic records,
“Good documentation constitutes an essential part of the regulated users should define which data are to be used
quality assurance system and is key to operating in compli- as raw data. All data on which quality decisions are based
ance with GMP requirements” (2). This statement can also should at least be defined as raw data.
be applied to GLP or any other quality system such as ISO • Certificates of analysis: Provide a summary of testing re-
17025 or ISO 9001. sults on samples of products or materials (1) together with
Chapter 4 also goes further in describing the types of the evaluation for compliance to a stated specification.
documents that are possible in a regulated organization: • Reports: Document the conduct of particular exercises,
• Site master file: This describes the GMP activities of a projects, or investigations, together with results, conclu-
manufacturer. We will not discuss this document in this sions, and recommendations.
column. From Chapter 4 (2) we can draw up some basic require-
• Instructions: Includes specifications, protocols, analytical ments for documentation for any quality system:
procedures, and standard operating procedures • Say what you do: Have an instruction to document a re-
• Records or reports: Evidence that instructions have been petitive task such as an analytical method or a standard
executed operating procedure (SOP)
These document types are shown in Figure 1. Of these, • Do what you say: Follow the instruction and if there are
the principle (2) describes the two main types of document any deviations from the procedure document them
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• Document it: Generate a record to problem? In our earlier discussion statement is relatively straightforward:
show that the instruction was followed. on Chapter 4 documentation (2) and It aims to describe the underlying
This chapter (2) also notes that shown in Figure 1, there is a clear de- principles for documenting GMP activi-
“The term ‘written’ means recorded, marcation between instructions and ties and to be able to reconstruct what
or documented on media from which records. However, in draft <1029> activities were performed, by whom,
data may be rendered in a human this distinction is blurred and both and when. When we come to the scope
readable form.” In Chapter 4 speak, instructions and records are inter- of the document we run into another
a document (instruction or records) mingled into generic “records.” This problem. The scope mentions that paper
does not exist only on paper, it can be is wrong and very misleading and electronic records can consist of
any medium as long as it can be con- raw data. Ah, the term “raw data” rises
verted into a readable format. Purpose and Scope from the deep again! Just as helpfully as
Chapter 4 goes further to discuss There are two paragraphs covering the EU GMP Chapter 4, the draft general
heterogeneous systems (hybrid systems scope and purpose of the general chap- chapter fails to define what raw data are.
where there are electronic records ter in the introduction. The purpose This is really helpful.
with handwritten signatures on paper
printouts) and homogeneous systems
(electronic signatures and electronic
records). The discussion is confused by
the mention of raw data in the records
section of Chapter 4, shown above.
However, the term raw data is not de-
fined in either EU or US GMP as it is
a phrase used in GLP (3,4). What does
raw data mean in a GMP context — es-
pecially as raw data can create other re- INNOVATION IN ATOMIC
cords? The GMP regulations are silent
on this subject.
SPECTROSCOPY:
LASER-INDUCED BREAKDOWN
USP Draft <1029> on GDP
Having set the scene, we can now
SPECTROMETERS
turn to the subject of this column and
review the draft USP general chapter
on good documentation practices. In Direct Sampling. All Elements. All Solid Materials.
overview, there is a preamble outlining
The ChemReveal™ LIBS Desktop Analyzer ofers the unique benefts of laser
the rationale for writing this general
induced spectroscopy in a robust, integrated package for rapid elemental
chapter and then the chapter itself is
analysis of solid samples.
divided into the following sections:
• Introduction with scope and purpose + Direct Analysis
• Principles of good documentation + Light Element Sensitivity
• Data collection and recording + Depth Profling
• Different types of GMP documents + Micro-scale Analysis
I will discuss each section in the + Minimally Destructive
sequence as it appears in the draft gen- + Material Fingerprinting
eral chapter.
For more information and to send a
sample, visit: www.tsi.com/ChemLogix
Preamble Problems
Our first problem comes in the pre-
amble for the general chapter, which
states “This chapter was created to
address a need for descriptions of
what constitutes good documenta-
tion, for example, records of all types
that are clear, accurate, and com-
plete.” OK, so far so good. However,
then comes “These records may in- UNDERSTANDING, ACCELERATED
clude protocols, procedures, reports,
and raw data” — now can you see the
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What is required is a discussion

about data and the associated metadata
for electronic records for both hybrid
EU GMP and electronic systems. What, you may
Chapter 4 ask, are metadata? The simplest answer
documentation is data about data, which is about as
useful as a chocolate teapot. A better
response is additional data that puts
the main data element in context. Let
me give you an example:
Site master
Instructions
When executed Records / • You have a spectrum generated by
file generate reports a spectrometer and saved as a file
named ABC123. You have a printout
of this file and on the printout there
Figure 1: Document types as defined by EU GMP chapter 4. Adapted with permission from is a link to the underlying file. Both
reference 2. the printout of the file and the file
itself are your data.
Principles of Good Documentation use predefined correction codes, for • However these data are useless as
This section is mainly a bulleted list example “WD” for wrong date. A bad there is no context. What is the anal-
of requirements for good documenta- day at the editorial office, perhaps? ysis? What is the spectrum? Who
tion that need to be interpreted for created it? Is there a reference spec-
the media on which the records are Data Collection and Recording trum? Therefore, we need more data
recorded. However, when reading the In the section on data collection and to put the spectrum into context and
bulleted points it is very clear that recording we reach the nadir of this understand why it was generated;
the focus of this general chapter and draft general chapter. The initial sec- this is the role of metadata.
the primary record medium is paper. tion lists four types of documentation, • Additional metadata are required
There is only implicit attention paid but there is no consideration of hybrid to put the data into context. For ex-
to hybrid and electronic systems, systems; it merely mentions instrument ample, sample information sufficient
but these are the majority of record printouts. Ah ha, you may exclaim but to uniquely identity the sample such
generating systems in a regulated it does — there is a mention that states as study, batch or lot number, or labo-
laboratory. The all-encompassing that these four formats “. . . are not lim- ratory sample number; instrument
statement that “Controls should be ited to.” Yes, that is correct. However, identity; method data that defines the
in place to protect the integrity of the as the majority of instruments used in instrument parameters used to ac-
records” is rather inadequate given the laboratories today are hybrid systems it quire the data; analysis data for how
industrial-scale falsification and fraud behooves a body, such as the USP, to in- the file was interpreted or analyzed
conducted by some companies in the clude them in such a list. Furthermore, to obtain the printout; reference spec-
past decade. For more detail on data it must state how to control all the re- trum or library reference used in any
integrity issues involving chromatog- cords generated by such systems: These comparison or calculations; any cal-
raphy data systems, see my upcoming records include both the signed paper culations performed on data derived
installment of the “Questions of Qual- printouts as well as the underlying elec- from the spectrum or spectra; speci-
ity” column in LCGC Europe (5). tronic records together with the linkage fications, if applicable, together with
One of the requirements in the between them. The draft chapter is si- the conclusion; audit trail data: who
draft general chapter is that “short- lent in this respect. created the file and when this was
hand notations are not allowed” We slide further into the mire as done plus any further manipulation
— obviously the author of this re- the section then discusses how to re- of the data. In addition, any changes
quirement has not visited a contract cord paper records and then describes to instrument or analysis settings
laboratory recently. In many contract what you should do for recording and during the work and the person who
research organization (CRO) labora- reviewing these paper records. How- made the changes.
tories there is a laminated sheet with ever, the section just adds a bald state- Furthermore, there is no men-
change codes posted on the walls ment that electronic records have to tion in the draft <1029> of the cri-
throughout the laboratory that detail comply with 21 CFR 11. The focus on teria for ensuring integrity of re-
all the reasons for change with a cor- paper as the primary record is so last cords: ALCOA+ criteria defined by
responding number to use when mak- century. Laboratories have moved on regulatory authorities. I discussed
ing a correction to a record. The use from paper. To avoid discussing hy- these in a “Questions of Quality”
of these codes is under the control of brid and fully electronic systems and column in LCGC Europe on a dis-
an SOP. However, in the next section the associated records is totally negli- cussion of fat finger, falsification,
of <1029> is a statement that you can gent and unprofessional, in my view. and fraud (6).
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• Attributable: Who acquired the data Table I: Suggested organization of draft Summary
or performed an action and when? <1029> instructions and records In reviewing the draft USP <1029>
• Legible: Can you read the data and Instructions Records general chapter on good documenta-
any laboratory notebook entries? Analytical Training
tion practices, this question crossed my
• Contemporaneous: Documented at methods documentation mind: Why was this general chapter
the time of the activity Standard oper-
ever written? What concerns me is
• Original: Written printout or obser- ating proce-
Equipment related that USP is offering training webinars
documentation
vation or a certified copy thereof dures now based on a poorly drafted general
• Accurate: No errors or editing with- Protocols Laboratory records chapter. Are pharmaceutical compa-
out documented amendments Retention of Certificates of nies and other regulated organizations
• Complete: All data including any records analysis so incompetent that they cannot pro-
repeat or reanalysis performed on Batch records vide training in such a basic subject?
the sample
Reports
• Consistent: All elements of the anal- References
Investigations and
ysis such as the sequence of events deviations
(1) In-Process Revision <1029> “Good
follow on and dates or time stamped Documentation Guidelines (New),”
in expected sequence Pharmacopeial Forum 40(3), May–
• Enduring: Not recorded on the back Figure 1 shows an innate logic: June (2014), www.usp.org.
of envelopes, cigarette packets, post- When instructions are executed, re- (2) European Commission Health and
it notes, or the sleeves of a laboratory cords are generated. This is not appar- Consumers Directorate-General,
coat, but in laboratory notebooks ent from this <1029> list above. What EudraLex: The Rules Governing
or electronically by the electronic <1029> should have done is placed the Medicinal Products in the European
lab notebook (ELN) and laboratory instructions first and the records sec- Union. Volume 4, Good Manufacturing
information management system ond, such as shown in Table I. Practice Medicinal Products for
(LIMS) used in the laboratory Nowhere in this section is there Human and Veterinary Use (Brussels,
• Available: Accessible for review and mention of the type and nature of Belgium, 2011), GMP Chapter 4,
audit or inspection over the lifetime the records required to underpin Documentation.
of the record each described type. For example, (3) Principles of Good Laboratory Practice
for laboratory records there is an (Organisation of Economic Co-opera-
Different Types of GMP Records all-encompassing “measurements,” tion and Development, Paris, 1998).
You may recall that a camel is often followed by “formulae and calcula- (4) Good Laboratory Practice for Non-
said to be an animal designed by a tions,” and ending up with “results Clinical Studies, 21 CFR 58, (U.S. Gov-
committee. So too is the USP docu- and conclusions.” ernment Printing Office, Washington,
mentation camel — the draft <1029> D.C.,1978).
does not distinguish between instruc- What Is Right with Draft <1029>? (5) R.D. McDowall, LCGC Europe, in press
tions and records or reports all are It would be unfair of me to just list (2014).
listed in no apparent or local order. the negative aspects of the draft USP (6) R.D. McDowall, LCGC Europe 25(4),
Perhaps the writers drew out of a hat <1029>, because it provides a good 194–200 (2012).
similar to a lucky dip. The document overview of how to record regulated
types are listed below in the order that activities on paper. However, it does
they are presented in the draft general not mention that pencil and typewriter R.D. McDowall
chapter to which I have added the correction fluid should never be used is the Principal of
document type in parentheses: for documenting GMP activities. McDowall Consulting
• Laboratory records (Records) and the director of
• Equipment related documentation Omissions from Draft <1029> R.D. McDowall Limited,
(Records) The omissions are far more serious, in and the editor of the
• Investigations and deviations my view: “Questions of Quality”
(Records) • Mixing instructions and records is column for LCGC Europe, Spectroscopy’s
• Batch records (Records) confusing and misleading. sister magazine. Direct correspondence to:
• Certificates of analysis (Reports) • It fails to define “raw data.” spectroscopyedit@advanstar.com
• Standard operating procedures • Its overwhelming focus on paper is
(Instruction) wrong and outdated.
• Protocols and reports (Instructions • It fails to provide adequate focus on
and Records) hybrid and electronic systems. For more information on this topic,
• Analytical methods (Instructions) • It fails to provide guidance on the please visit our homepage at:
• Training documentation (Records) underlying records required to sup- www.spectroscopyonline.com
• Retention of records (Instruction) port the record types listed.
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Chemometrics in Spectroscopy
Units of Measure in Spectroscopy,
Part II: What Does It Mean?
Now that we have shown the relationships between different units for concentration, we con-
tinue by demonstrating their effects on the data we collected and used for our examples. We
also begin our discussion on the ramifications and consequences of our findings.
Howard Mark and Jerome Workman, Jr.
T his column is the next continuation of our dis-

cussion of units on calibration, as described in
part I of this series (1) and examined through
the use of the classical least squares (CLS) approach
to calibration (2–13). In this column, we continue
units of measurement have different relationships to
the spectral values, for reasons having nothing to do
with the spectroscopy. One of the conclusions of this
finding is that it disproves the usual, although inevi-
tably unstated, assumption that different measures
the numbering of equations, figures, and tables from of concentration are equivalent except, perhaps, for a
where we left off in part I (1). constant scaling factor. Furthermore, it is clear that if
In our previous columns (1,9) we confirmed that two measures of concentration are nonlinear with re-
the volume percent is the physical quantity that spect to each other, then a third measurement, such as
agrees with the spectroscopic evaluation of the con- a spectroscopic measurement, that is linear with re-
tribution of the components of a mixture to the spec- spect to one measure must be equally nonlinear with
trum of the mixture. We also demonstrated that the respect to the other measure.
nature of the CLS algorithm allowed us to determine We also showed how a concentration measurement
two important properties of the conversion of “con- unit can be constructed so that it is indeed equiva-
centration” between different units. lent to the volume percent, except for a scaling factor.
We determined in Table I from part X of the previ- The key to this conversion is to multiply the volume
ous subseries (11), as well in Table IV from part XI (12), percentage by a unit that has a volume in the denomi-
that there is not a unique conversion between concen- nator — examples include weight/unit volume and
tration values expressed in different units. We also molarity (moles/unit volume).
showed, in Figures 1–3 from part I of this subseries (1), One of the more common measures of concentra-
that there is not a linear relationship between concen- tion used in conjunction with spectroscopic analy-
tration when expressed in different units. sis, however, is weight percent (that is, weight/unit
Thus, the data (Figures 1–3 from part I of this weight, which is not included among the measure-
subseries and Figure 7–9 here) show that different ment units that are equivalent to volume percent).
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Table I from part X (11), as we This nonequivalency has nothing to do with

previously noted, shows that a
value for volume percent of a given the spectroscopy; it is purely a matter of ele-
component can correspond to a
wide range of weight percentages
mentary physical chemistry.
and vice versa: A given value of
weight percent can correspond to measure exactly” method of making such poor performance would
a correspondingly wide range of ing the samples). This nonequiva- be rejected for consideration as a
volume percents. Here, Figures lency has nothing to do with the reference laboratory), larger than
7–9 show the same effect: Many spectroscopy; it is purely a matter virtually any instrumental error,
values for concentration calcu- of elementary physical chemistry, and larger than any other error
lated from the spectra using the and is the source (or at least one source we normally encounter.
CLS algorithm, which stands as a of the sources) of what we used to Yet this error source has previously
surrogate for the volume fraction, call matrix effect in undergraduate been hidden and undetected, despite
correspond to a given value of the analysis courses. In those courses, its role as the largest error source in
concentration expressed as weight matrix effect was typically con- our chemometric calibration work.
percent units. This variability does sidered small, but we see in Table When you think about it, you realize
not depend on the concentration I from part X (11) and in Figures that one of the problems a calibration
of the analyte, but instead on the 7–9 that it can be, and in our ex- algorithm has to solve when con-
composition of the rest of the mix- periments indeed is, very large — fronted with data where the “wrong”
ture, affecting the volume fraction being, in our case, a source of er- units are used for the analyte values,
and spectroscopic concentrations, rors as large as 5–10%. This error is how to determine the value of that
whereas the weight percents are source is larger than any other we analyte when two (or more) samples
essentially constant at each level typically encounter in spectro- are described as having different
(note that they are not exactly scopic analysis. It is much larger values of the analyte by the scientist
constant, because of the use of than any of the usual laboratory performing the calibration (that is,
the “dispense approximately then error sources (a laboratory show- different reference values) while the
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(a)
(a)
100 100
90 90
80 80
70 70
60 60
Weight %
Weight %
50 50
40 40
30 30
20 20
10 10
0
0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
0 10 20 30 40 50 60 70 80 90 100
CLS values
CLS values
(b) (b)
100
100
90
90
80
80
70
70
60
Weight %
60
50
Weight %
50
40
40
30
30
20
20
10
10
0
0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
0 10 20 30 40 50 60 70 80 90 100
CLS values
CLS values
Figure 7: Plot of CLS values versus weight percent and mole percent, Figure 8: Plot of CLS values versus weight percent and mole percent,
for toluene. (a) Weight percent versus CLS values; (b) volume percent for dichloromethane. (a) Weight percent versus CLS values; (b) volume
versus CLS values. percent versus CLS values.
spectroscopic data are telling the algorithm that they are the units that the concentration was to be measured
the same. And, of course, the opposite situation invari- in. Underlying this lack of interest was a hidden and
ably also occurs, that the spectroscopy indicates that the unstated assumption, namely that the units used were
analyte concentrations are the same, while the reference immaterial because different measures of concentra-
values indicate that they are different. tion were expressing the same underlying quantity,
It is a testimony to the power of the mathematics that and the only difference between different units was a
despite the large magnitude of this error source, the scaling factor.
algorithms can indeed unravel the effects and (most However, that this is not so is clearly seen in Fig-
of the time) create models for describing the mixtures ures 1–3 from part I (1). We noted at the time we
with reasonable, but not complete, accuracy. examined these figures that because there are many
Classically, the underlying quantity that chemical lines representing the relationship between two dif-
analysis attempts to determine has been the concen- ferent units, that relationship cannot be 1:1. Any line
tration of the analyte. Little mention was made of that is drawn either vertically or horizontally on the
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plot would represent a single value these phenomena on the calibra- percent and volume percent, or
of the concentration as expressed tions produced by chemometric equivalently, between weight per-
in one unit, but that value of algorithms. cent and absorbance. The surface
concentration would correspond We have previously described meaning of those figures is that
to a number (indeed, an infinite the development of the multiple because of those nonlinear rela-
number) of values of concentra- linear regression (MLR) algorithm tionships, at best a different coeffi-
tion when expressed in the other (14–16). We also showed that a cient would be needed for samples
unit, corresponding to different correction factor for the presence with different analyte concentra-
compositions of the “matrix.” It is of an interfering absorbance band tions to convert the absorbance
therefore impossible for there to be and the way measurements at a value to a concentration value.
a linear relationship, or indeed any different wavelength can correct In the presence of interfering
type of one-to-one relationship, an absorbance reading at the ana- absorbance bands, the situation be-
between the two different units of lytical wavelength. Unstated, al- comes even more complicated. With
measure because of this many-to- though implicit in the assumption linear data, ordinarily a single cor-
one correspondence. of Beer’s law, is that all absorbance rection factor would be needed to
We also see in Figures 1–3 from readings are in fact linear with calculate from the absorbance read-
part I (1) that not only are the lines respect to the concentration of the ing at one wavelength the correction
representing each value of constant analyte, and also with respect to to the measured absorbance at the
composition of the matrix curved, any materials in the sample that appropriate analytical wavelength.
but also these lines have variable contain interfering absorbance As we described in the discussions
spacing between them despite bands. Thus, the relationships be- of Figures 1–3 from part 1 (1), how-
the fact that in those figures the tween different units is critical in ever, the curves describing the re-
compositions of the matrix varies interpreting the results from an lationships between different units
by constant amounts between two MLR calculation. are not evenly spaced, for constant
adjacent lines. This variable spac- The main relationship that Fig- differences between the correspond-
ing has significant consequences ures 1–3 from part I (1) show is the ing sample matrixes. This means
when considering the effects of nonlinear relation between weight that the correction factor is differ-
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In other words, if all was linear, then

the theoretical correction for interfer-
(a) ence would be all that was needed to
get accurate results. In the face of the
fact that nearly all relationships be-
100 tween optical response and concentra-
tion are nonlinear, this nonlinearity of
90 the relationships means the correction
80 also needs a correction, and very likely
the correction to the correction also
70 needs a correction, as well.
60 Looking at typical calibration
Weight %
results, we should have always been

50 aware that something anomalous
40 was happening. What sorts of
calibration results would we expect
30 from properly-behaving data? Tomes
20 dealing with the theory of calibra-
tion (17) tell us that as meaningful
10 variables are added to a calibra-
tion equation, the calibration error
0
should decrease, and when suffi-
0 10 20 30 40 50 60 70 80 90 100 ciently many variables are included
CLS values in the calibration model, the error
of calibration should decrease and
(b) relatively abruptly reach the funda-
mental noise level when sufficiently
many variables are included. From
100 that point on, any new variables that
are added to the calibration model
90
should have no effect, and statistics
80 for that new variable should show
70 that it is not statistically significant.
How many variables (considering
60 “variables” to be either absorbances
Weight %
50 at various wavelengths for an MLR

model, or weights for factors for
40 a principal component regression
30 [PCR] or partial least squares [PLS]
model) could be included in a near-
20 infrared (NIR) model when this
10 happens? Calibration theory plus
mathematical theory also tells us
0
that. There should be no more vari-
ables in a calibration model than
0 10 20 30 40 50 60 70 80 90 100 there are actual physical variables
CLS values that affect the absorbance of the
samples. Generally, that should be
Figure 9: Plot of CLS values versus weight percent and mole percent, for n-heptane. (a) Weight a fairly small number; few sample
percent versus CLS values; (b) volume percent versus CLS values. types include more than four or
five components that absorb ap-
ent for different concentrations of conversion between spectral absor- preciable amounts of the incident
the interferences as well as for the bance and concentration, therefore, radiation, so that would require
analyte. Therefore, even the correc- requires a coefficient that depends four or five variables in the model,
tion for interferences is not a con- not only on the amount of analyte, plus maybe one more to account for
stant coefficient, but the correction but also on the amount of each of the effects of optical scattering in
factor also needs a correction. The the interferences. powdered samples.
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How many variables are typically thickness of the sample in units of (12) H. Mark and J. Workman, Jr.,
found in NIR calibrations? While centimeter of the measured sample Spectroscopy 27(10), 12–17
experience indicates that occasion- at a specific concentration. With this (2012).
ally a model contains two or four assignment of units, it can be seen (13) H. Mark and J. Workman, Jr., Spec-
variables, much more often they are that the units on the right-hand side troscopy 28(2), 24–37 (2013).
found to contain 8–20 variables, with of equation 14 cancel, as they must (14) H. Mark, Principles and Practice
a broad maximum at around 12. And to match the dimensionless quantity of Spectroscopic Calibration,
rather than rapidly decreasing to an (absorbance) on the left-hand side. (John Wiley & Sons, New York,
abrupt transition to errors being at Later authors (19) generalized this 1991).
the noise level, the calibration error concept, noting that the fundamen- (15) J. Workman, Jr., and H. Mark,
corresponding to all those variables tal requirement was for the units on Spectroscopy 7(1), 44–46 (1992).
continues a long, slow decrease that both sides to match, but that various (16) J. Workman, Jr., and H. Mark,
often never terminates (or at least, sets of units could be used as long Spectroscopy 7(3), 20–23 (1992).
not within the range of the maxi- as this restriction was met. It seems (17) N. Draper and H. Smith, Applied
mum number of variables included). likely that the specifications of the Regression Analysis, 3 Ed. (John
Now we know why that happens. units by Harrison and colleagues Wiley & Sons, New York, 1998).
Rather than fitting the data to (18) were intended to provide a (18) G.R. Harrison, R.C. Lord, and J.R.
discrete compositional or physical single, universal set of absorbtivi- Loofbourow, Practical Spectros-
variations of the data, the calibra- ties for common analytes that could copy (Prentice-Hall, New York,
tion is fitting the higher factors be published in tables so that other 1948).
of the spectral data, not to the scientists could use them to perform (19) J.D. Ingle and S.R. Crouch, Spec-
changes of the spectra caused by analysis without having to redeter- trochemical Analysis (Prentice-
physical or chemical variations, but mine them every time they wanted to Hall, Upper Saddle River, New
to the nonlinearities between the measure those analytes. Jersey, 1988).
spectra and the analytical values
the calibration is presented with, References
Jerome
to try to fit the spectra to. And to (1) H. Mark and J. Workman, Jr., Spec-
Workman, Jr.
be sure, the residual errors because troscopy 29(2), 24–37 (2014).
serves on the Editorial
of those nonlinearities do indeed (2) H. Mark and J. Workman, Jr.,
Advisory Board of
continually decrease as each new Spectroscopy 25(5), 16–21
Spectroscopy and
spectral variable is included in the (2010).
is the Executive
calibration model. This gives the (3) H. Mark and J. Workman, Jr.,
Vice President of
calibration a better fit to the data, Spectroscopy 25(6), 20–25 Engineering at
but also leaves smaller and smaller (2010). Unity Scientific, LLC, (Brookfield,
residual nonlinearities to be fit (4) H. Mark and J. Workman, Jr., Connecticut). He is also an adjunct
by further factors; the underlying Spectroscopy 25(10), 22–31 professor at U.S. National University
noise level is generally not reached. (2010). (La Jolla, California), and Liberty
When all is said and done, we (5) H. Mark and J. Workman, Jr., University (Lynchburg, Virginia). His
also note that very early references Spectroscopy 26(2), 26–33 e-mail address is JWorkman04@gsb.
clearly define the requirement for (2011). columbia.edu
concentration in the Lambert-Beer (6) H. Mark and J. Workman, Jr.,
equations to be gram-molecular Spectroscopy 26(5), 12–22
Howard Mark
weight per liter (18). This relation- (2011).
serves on the Edito-
ship between measured spectral (7) H. Mark and J. Workman, Jr.,
rial Advisory Board
signal and concentration of a mol- Spectroscopy 26(6), 22–28
of Spectroscopy and
ecule is most often expressed as: (2011). runs a consulting ser-
(8) H. Mark and J. Workman, Jr., vice, Mark Electronics
A = εcl [14] Spectroscopy 26(10), 24–31 (Suffern, New York).
(2011). He can be reached via
Where ε is the molar absorbtivity (9) H. Mark and J. Workman, Jr., Spec- e-mail: hlmark@nearinfrared.com
(referred to as molar extinction coef- troscopy 27(2), 22–34 (2012).
ficient by earlier physicists) in units (10) H. Mark and J. Workman, Jr.,
of L · mol-1 · cm-1; c is the concentra- Spectroscopy 27(5), 14–19
tion of molecules in the spectrometer (2012). For more information on
beam in units of (11) H. Mark and J. Workman, Jr., this topic, please visit:
mol · L-1 (note: this is a scaled volume Spectroscopy 27(6), 28–35 www.spectroscopyonline.com
fraction unit); and pathlength l is the (2012).
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SPECTROSCOPY SPOTLIGHT
Improving Drug Formulation

with Raman and IR Spectroscopy
The physicochemical properties of drugs are often very diverse and challenging to analyze. We recently spoke
with Dr. Lynne Taylor of the Department of Industrial and Physical Pharmacy at Purdue University, and the
2014 Coblentz Society Craver Award winner, about her ongoing research using Raman and infrared (IR) spec-
troscopy to study drugs and drug excipients — and the interactions of the two. Here, she discusses the various
avenues of her research, including crystallization and drug-rich nanodroplets.
How did you become involved in im- ent solid-state forms of pharmaceutical the correct therapeutic effect. If the salt
proving drug delivery through studying compounds. What are the advantages of converts back to the free form, it may
the physicochemical properties of drugs Raman spectroscopy for those analyses? not dissolve fast enough. Excipients can
and excipients? Taylor: Different solid state forms of change the local pH in a tablet and cause
Taylor: After qualifying as a pharmacist drugs often have unique Raman spectra, a drug to transform back to the free
in the United Kingdom, I worked for a so that Raman spectroscopy can be used form. You can’t study this process with a
year in a hospital in Zimbabwe. I saw a to identify and even quantify which poly- solution chemistry technique, you have
lot of substandard medicines being used, morph or other solid state forms are pres- to study the drug in the solid formula-
and also had to make several different ent. With fiber-optically coupled Raman tion. Raman and IR spectroscopy are
types of medicines including creams systems, this means that you can monitor ideal for this purpose because the salt
and cough syrups, since there were so transformations between different forms and free form of the drug have different
many drug shortages. This sparked my during processing operations, or even spectra. So you can mix the drug powder
interest in formulation, and I returned to mimic the dissolution process that would with various excipients, expose them to
the UK to undertake a PhD in this area happen in the stomach, and see how the different relative humidity conditions,
at the University of Bradford. The longer transformation kinetics vary with differ- and find out which excipients will cause
I worked in the area, the more I realized ent conditions. Most drugs are aromatic the drug to convert to the free form and
that a medicine is more than a molecule, compounds, whereas most excipients are which excipients have no effect. Obvi-
and that how you formulate a drug is key not, so there are virtually always some ously, for the final formulation, it is best
to achieving a good therapeutic outcome. unique drug peaks that are Raman ac- to select those excipients that don’t cause
tive and are not masked by excipients. these types of changes.
What are the biggest challenges you have This means that Raman spectroscopy is
faced in this research? a great method for evaluating the drug in You have also published quite a bit of
Taylor: I think the biggest challenge is the presence of excipients, and even in the research on crystallization. Can you
the diversity in properties of drugs and final dosage form. please tell us about your research in
excipients. For example, a drug can exist that area? What spectroscopic tech-
in several different solid state forms, and
In a paper you published in 2009 (1), you niques in addition to Raman were used
can undergo transformations between used infrared (IR) and Raman spectros- in that research?
the different forms with consequences copy to investigate the contributing fac- Taylor: I am actually very interested
for the effectiveness of the dosage form. tors in the process of disproportionation in preventing drugs from crystallizing,
Excipients can have a huge impact on whereby salt converts back to the free which means that I have to study crystal-
the rate of these transformations, but at form of a drug. Can you please tell us lization! As mentioned previously, many
the moment we can’t predict these ef- about that work and what the results of the new drugs that are being discov-
fects. So, you can work with one drug meant for your next project? ered are not very water soluble. An alter-
and think that you understand the sys- Taylor: Drugs are often produced as native to making salts is to destroy the
TOM FULLUM/GETTY IMAGES
tem, but get completely different results salts since this makes them dissolve crystal lattice and make an amorphous
when you switch compounds. faster. Many drugs are not very soluble, solid. Amorphous solids are high energy
and it is very important that they dis- forms, and can dissolve to produce solu-
You have used Raman spectroscopy to in- solve fast enough from tablets after tions with a temporarily higher solution
vestigate transformations between differ- they are swallowed, so that they have concentration than the crystalline form.
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The trick is to prevent crystallization which has been immensely rewarding. ily responsibilities (most of the time!).
both in the solid formulation and from My advice would be to find people with
the solution produced following disso- complementary interests to interact with, References
lution. Normally, polymers are added as rather than working in isolation. Net- (1) P. Guerrieri and L.S. Taylor, Pharmaceutical
crystallization inhibitors, but we don’t working is very important. The other im- Research 26(8), DOI: 10.1007/s11095-009-
understand much about how polymers portant piece of advice that I can give, is 9918-y (2009).
inhibit crystallization, or how to find that young scientists should try and stay (2) D. Wanapun, U.S. Kestur, D.J. Kissick, G.J.
the best polymer for a given drug. We focused. Today’s working environment Simpson, and L.S. Taylor, Anal. Chem. 82(13),
routinely use Raman spectroscopy to can be incredibly demanding, making 5425–5432 (2010).
monitor crystallization kinetics, but also work–life balance challenging. By staying (3) G.A. Ilevbare, H. Liu, J. Pereira, K.J. Edgar, and
have used IR spectroscopy to study drug– focused, I think it is possible to progress L.S. Taylor, Mol. Pharmaceutics 10(9), 3392–
polymer hydrogen bonding interactions well in one’s career, while balancing fam- 3403 (2013). ◾
in solid drug–polymer blends, and in-
line ultraviolet spectroscopy to mea-
sure solution concentration versus time
profiles during dissolution of the amor-
phous formulation. In collaboration with
RAISING
my colleague, Professor Garth Simpson
in the Chemistry Department at Purdue,
we are also using second-order nonlin-
ear optical imaging of chiral crystals for THE BAR
the sensitive detection of crystallinity in
amorphous formulations (2).
IN RAMAN
What do you plan on researching next?
SPECTROSCOPY
Taylor: Recently, we have been studying
the solution phase behavior of poorly Introducing TSI’s full line of
water soluble drugs. Interestingly, when high-performance, easy-to-use
amorphous drug–polymer blends are Raman spectrometers boasting:
dissolved, in some cases we have ob- + Hand held, portable, and laboratory
served the spontaneous formation of bench top instruments
drug-rich nanodroplets (3). We plan to + Research-grade performance
at an afordable price
study the physicochemical properties of
+ Fast material identifcation with
these nanodroplets and to evaluate how shortest sample times
they can be used to improve drug deliv- + Repeatable instrument to instrument,
ery. I am also very interested in devel- database transferable across all platforms
+ Excellent fuorescence rejection
oping new excipients based on polysac-
+ The right material ID the frst time
charide derivatives. I have a very fruitful
collaboration with Professor Kevin Contact TSI for the right Raman
Edgar, a renowned polymer chemist at instrument for your needs or
visit: www.tsi.com/RAMAN
Virginia Tech. Together we are explor-
ing the properties of a variety of novel
polysaccharide derivatives, in particular
as crystallization inhibitors.
As a young scientist you have a great list

of accomplishments ranging from your
publication number to the positions
you’ve held and awards you’ve received.
Do you have any advice for scientists just
starting out in this field?
Taylor: I’ve been fortunate enough to
work in a few different countries includ-
ing the UK, Zimbabwe, Sweden, and the
United States. I think these experiences
have made me very open to collaborating
with people in different research areas,
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How Trace Elemental Analysis

Provides Important Insight into
Wine Chemistry
The elemental composition of red wine was studied with inductively coupled plasma–mass spec-
trometry (ICP-MS). The impact of storage and packaging as well as the role of geographic origin on
the elemental content were shown. While metal content can be related to the location of the vine-
yard, various aspects of wine making can also influence the elemental composition. For example, we
have shown that wine packaging and storage temperature can change the elemental composition of
wine after a period of six months.
Helene Hopfer, Jenny Nelson, Thomas S. Collins, Hildegarde Heymann,

and Susan E. Ebeler
T he analysis of alcoholic beverages, such as wines and

distilled spirits, is challenging from an analytical point
of view because of the many different functional classes
that are present. To obtain a complete picture of the compo-
sition of these products and answer food safety and quality
food and wine products. Projects facilitating these instruments
have been used to study the fate of important food compo-
nents during processing; examples of these projects include
phenotypic profiling in breeding trials and developing rapid
quantitative methods for various taint compounds for the food
questions, a combination of analytical techniques is needed. and wine industry.
In addition to the analysis of organic components such In this article, we specifically focus on trace elements and
as acids, sugars, flavonoids, and the important aroma and provide examples of how they yield additional and otherwise
flavor compounds, the analysis of elemental composition is not accessible insight into beverage properties. Our examples
an important piece for the evaluation of quality. At the Food highlight different aspects of wine processing and how el-
Safety and Measurement Facility at the University of Califor- emental fingerprinting could provide valuable information
nia (UC), Davis, a cross-platform approach is taken for the about the geographical origin of a food or beverage (study 1).
analysis of food and beverage products, including the analysis We also show how different steps in the production of wines
of the volatile, nonvolatile, and elemental portions of foods impact their elemental composition (study 2).
and beverages. The available techniques, such as ultrahigh- Understanding the elemental profile of wines is important
pressure liquid chromatography–quadrupole time-of-flight from several standpoints. Firstly, some elements are regulated,
mass spectrometry (UHPLC-QTOF-MS), UHPLC–tandem with most countries following the maximum legal limits es-
mass spectrometry (MS-MS), high performance liquid chro- tablished by the International Organization of Vine and Wine
matography–mass spectrometry (HPLC–MS), gas chromatog- (OIV) (1). Examples for these are As, B, Br, Cd, Pb, and Zn,
raphy–mass spectrometry (GC–MS), GC–MS-MS, inductively for which maximum legal limits in the upper parts per mil-
coupled plasma–mass spectrometry (ICP-MS), and inductively lion (mg/L) to mid parts per billion (µg/L) have been defined.
coupled plasma–optical emission spectrometry (ICP-OES), are Secondly, many elements impact the quality of vine and
used in both nontargeted and targeted analyses of different wine, as they are macro-, micro-, and trace nutrients for the
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soil composition, and the reflection of

these differences in plants grown in the
10 soil, it has been proposed that some ele-
ments in a final food product could be
representative of the origin. Previous
research has shown that the elemental
composition of soil and wine made of
grapes grown on that soil are not well
5 correlated (3), and this discrepancy
2
PC 2.25%
1 could be explained by the numerous

0 changes in the elemental fingerprint
due to the wine-making process, includ-
3 ing filtration, clarification, additions,
and packaging and storage conditions
4 (4–6). Only with a clear understanding
of how each wine-making step affects
the elemental content, and how large
these changes are within one variety,
one winery, and one wine-making re-
–10 gion, could an elemental fingerprint be
useful for tracing back the geographical
–5 0 20
origin of a bottle of wine. As a first step
PC 1.51%
in developing this understanding, we
evaluated the effect of growing regions
Figure 1: Principal component analysis (PCA) showing the separation because of elemental
on the elemental composition of wines
differences in wines coming from the five vineyards. Circles around the means represent the 95%
and further studied the effect of pack-
confidence intervals obtain via a bootstrapping algorithm.
aging and temperature on changes in
elemental composition that may occur
during wine storage.
51
V 208
Pb 52
Cr 63
Cu 118
Sn Experimental
Screw cap 10 ºC For all studies an Agilent 7700x ICP-MS
(high fll 20 ºC instrument was used. Instrument set-
height) 40 ºC tings are listed in Table I.
Screw cap 10 ºC
(low fll 20 ºC
For the first, currently ongoing study,
height) 40 ºC 65 red wines were sampled from five
Natural cork 10 ºC commercial wineries. All wines came
20 ºC from five vineyards located within 40
40 ºC miles (64 km) of each other, and were
Bag-in-box 10 ºC located in two American viticultural
20 ºC
40 ºC
areas (AVAs).
The second study looked at changes
Observed range
and (ppb) 13.9 34.7 4.3 8.8 14.1 23.0 11.0 152.7 0.1 16.0 in red Cabernet Sauvignon wine be-
cause of packaging and storage condi-
tions. The samples were part of a larger
Figure 2: Elemental differences in the same red Cabernet Sauvignon wine because of storage research project and also included vol-
conditions and packaging configuration. Error bars shown for each element represent the atile, polyphenol, and sensory profil-
honestly significant differences (HSDs) from the Tukey test. ing. ICP-MS was used to characterize
the elemental changes in the wines.
vine plant or are used in agrochemi- monitored during wine making (2). Ex- The same Cabernet Sauvignon wine
cals. Some elements found in wine are amples for this are Cu and Fe, which can (vintage 2009, Northern California)
the result of environmental deposition. act as oxidation catalysts, and can also was filled into four packaging con-
Examples include Pb because of its use cause haze formation in wines, similar figurations (3-L bag-in-box, 0.75-L
in gasoline, or Na in vineyards located to Zn or Al. glass bottle with a natural cork, two
near coastal areas (2). Additionally, Lastly, elemental fingerprints could be treatments with a 0.75-L glass bottle
some elements have detrimental effects useful in the determination of geograph- with an aluminum screw cap, and a
on wine stability and need to be closely ical origin. Based on the differences in tin-PVDC liner, differing in fill height
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[headspaces of 5 and 15 mm]). All significant differences [HSD]). Princi- ity is coming from the vineyard. In this
packaging configurations were stored pal component analysis (PCA) was used ongoing study, we profiled 65 red wines
at 10 °C, 20 °C, and 40 °C for a pe- as an unsupervised multivariate data from five different vineyards, from two
riod of six months before the various reduction technique to gain further different AVAs. Initial results showed
analyses took place. For more details, insight in the differences among sam- that 39 elements differed significantly
we refer the reader to the respective ples and determining the variables that in their concentrations among the sam-
publications (6,7). explain most of the observed variance ples from the five different vineyards (P
For a ll ICP-MS measurements, among the samples. Approximately, ≤ 0.05). Using the significant elements,
wine samples were diluted in dupli- 95% confidence intervals (CI) were cal- samples are readily separated in a PCA
cate (study 1) and triplicate (study 2) culated via a bootstrapping algorithm as shown in Figure 1. More than 75% of
1:3 with 5% nitric acid to decrease the to obtain variability measurements for the total variance is explained within the
ethanol content to around 4% (4,8–11). each of the vineyards. first two principal components. Wines
An internal standard solution (1 mg/L from vineyards 1 and 5 as well as wines
in 1% nitric acid) covering the m/z Results and Discussion from vineyard 2 and 3 show more simi-
range from 6 to 209 was constantly Study 1 larity to each other than to wines from
fed into and mixed with the sample The elemental composition of grapes the other vineyards, as their confidence
stream via a mixing tee. Monitored el- is a reflection of both exogenous and intervals overlap. Wines from vineyard
ements were calibrated in a range be- endogenous factors, coming from both 4 differed significantly from all other
tween 0–500 μg/L in matrix-matched natural sources and human interven- vineyards as the confidence intervals
solutions (4% ethanol, 5% nitric acid). tion. The use of a multielement fin- around vineyard 4 did not overlap with
Elements that were detected above gerprint for the determination of geo- any wines of other vineyard origins. El-
their respective detection limits were graphical origin requires knowledge ements that contribute to the observed
used for data analysis, which included about the variability of said fingerprints separation include rare earth elements
multi- and univariate analysis of vari- within one region, as well as within as well as Ni, Ca, and Mg. However, a
ance to determine statistical significant wineries, countries, and continents. full understanding of the effects of geo-
differences, as well as Tukey’s test for As a very first step, one needs to estab- graphic origin on metal content of wines
multiple means comparison (honestly lish how much of the elemental variabil- will also require the analysis of the vine-
Wear Metals Soil Analysis
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Table I: ICP-MS instrument settings used in the studies as a welding alloy and in small fittings (15).
Previous studies report Cr concentrations in wine between
Mode Helium mode and no gas mode
7 μg/L and just below the legal limit of 100 μg/L. The levels
RF power 1550 W we found were at the lower end of this spectrum with lower
Nebulizer Micromist pump rate: 0.1 rps levels in the bag-in-box treatments compared to the bottle
Quartz double-pass cooled to treatments. Cr showed a smaller temperature impact, and its
Spray chamber
2°C presence in wine could be the result of contamination because
of storage in stainless steel containers due to the use of Cr as
Carrier gas Ar, 1 L/min an alloy element, or glass bottles, where chromium oxide is
Flows used as a bottle pigment (2,12).
He, 4.3 mL/min and 10 mL/min For the last two elements, Cu and Sn, larger differences
Collision cell gas
for As and Se between the 12 treatments were found. While the first three
6Li: m/z 7–39
elements (V, Pb, and Cr) showed an approximately twofold
Mass range covered by change, Cu and Sn were more affected by the different stor-
89Y: m/z 43–95
each internal standard 115In: m/z 101–137
element
age and packaging conditions — both elements showed at
209Bi: m/z 139–238
least a 10-fold change. Cu levels were most affected by stor-
age temperature, with increasing temperature the Cu con-
yard soils. This analysis is needed to fully understand and centrations decreased. This is most likely because of metal
explain the sources for the observed differences in elemental complexes with wine components precipitating at higher
composition of the wines. temperatures, as described by others (2,13). Different routes
for Cu in wine have been described before: Copper sulfate is
Study 2 used as a fungicide in vineyards to reduce fungal pressure,
The last step in the wine-making process is packaging and but can also be used in the winery for removal of hydrogen
storage of the finished wine. Because of the use of many differ- sulfide off-f lavors. Another source for Cu in wine is the
ent packaging configurations as well as storage conditions, it use of brass equipment in the wine-making process (2,12).
is important to understand how different packaging types can The presence of Sn in wine has never been reported before,
change the wine composition. Besides changes in the sensory and it is not regulated in wine with the exception of Croatia,
properties, various chemical changes have been described, which limits Sn levels in wine with 10 mg/L (12). Sn was only
including volatile and nonvolatile changes (7). found in the screw-capped samples, making its origin most
However, the elemental composition can also be changed likely to be the tin-PVDC liner inside the screw cap. This
because of storage and packaging conditions, as shown by theory would also explain the increase in Sn with increasing
our group (6). Storing the same wine for six months in differ- temperature, a phenomenon in contrast to all the other ele-
ent packaging configurations and at different temperatures ments. With increasing temperature the wine expands and
led to significant changes (P ≤ 0.05) in five elements as shown pushes against the liner inside the screw cap, thus, more Sn is
in Figure 2. The elements V, Pb, Cr, Cu, and Sn showed sig- leached into the wine over time (6).
nificant differences between the 12 treatments because of Based on these findings one important question re-
both packaging and temperature effects. However, the mea- mains: If storage conditions, including packaging type
sured levels were below the regulatory maximum levels if and temperature, are able to change the elemental com-
available: OIV (1): Cu 1 mg/L, Pb 0.15 mg/L; Croatia (12): Cr position of wine, what are the consequences for the shelf
0.1 mg/L, Sn 10 mg/L. life of wine when these elements are leached into the wine
Higher V levels were found in the screw-capped samples over time? Especially the effect of increased levels of the so
with a high fill level, while all other packaging types showed called wine-sensitive elements (Al, Cu, Fe, Si, and Zn) on
lower concentrations of V. Additionally, with increasing stor- the wine properties needs to be assessed, as these elements
age temperature, V decreased, most likely because of precipita- have been shown to impact wine stability and the sensory
tion of metal complexes with wine constituents such as poly- properties of wine during wine making (16). A similar
phenols, peptides, and polysaccharides (2,13). The presence behavior can be expected during wine storage when these
of V in wine has been previously reported by Almeida and elements are present.
colleagues (14) as a result of the use of V in stainless steel wine- The elemental composition of wine can be changed by vari-
making equipment. ous factors throughout the grape growing and wine-making
For Pb, slightly higher levels were again found in the high- process. We showed that storage conditions can alter the el-
fill screw caps, with decreased levels in the wines stored at emental fingerprint of wine. Some of the elements that dif-
higher temperatures. Because of its use in gasoline before the fered because of the storage conditions (for example, Cu) are
1980s, Pb is present in soil and the atmosphere so its presence so called wine-sensitive elements, meaning that they impact
in wine can be partially explained by this fact. However, one wine stability and quality during wine making, and it can be
study monitored Pb throughout the wine-making process and expected they have a similar impact during storage.
found that up to two-thirds of the final Pb concentration in The use of an elemental fingerprint for the determina-
wine comes from within the winery, because of the use of Pb tion of geographical authenticity requires a deep knowl-
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edge about the wine-making process and how it can change (15) C.M.R. Almeida and M.T.S.D. Vasconcelos, J. Agric. Food Chem. 51,
the elemental composition. Wines coming from different 3012–3023 (2003).
vineyards differ in their elemental composition, but the (16) M. Aceto, in Reviews in Food and Nutrition Toxicity, R. Watson and V.
question remains whether the observed differences are a Preedy, Eds. (Taylor & Francis, London, 2003), pp. 169–203.
result of the different vineyards or if the processing winer- (17) M.D.M. Castiñeira Gómez, R. Brandt, N. Jakubowski, and J.T. Andersson,
ies contribute to these differences as well. Based on previous J. Agric. Food Chem. 52, 2953–2961 (2004).
research, it can be assumed that wine making has an impact
on the elemental composition of wine (4,5,14,15,17). Thus, Helene Hopfer, PhD, is a postdoctoral scholar in the
the traceability of individual vineyards from the finished Department of Viticulture and Enology at the University of California in
wine is highly dependent on how strong the winery impact Davis, California. Jenny Nelson, PhD, is an application special-
is. This important piece of information is currently under ist in the Agilent Food Team in Santa Clara, California and an assistant
investigation in our laboratory. adjunct professor in the Department of Viticulture and Enology at the
University of California. Thomas S. Collins, PhD, is the direc-
Conclusion tor of research in the Food Safety and Measurement Facility at the
The measurement of elemental profiles of food and bever- University of California. Hildegarde Heymann is a professor of
age products provides important information to increase and Enology at the Department of Viticulture and Enology at the University
improve food and beverage quality. Besides wine-making of California. Susan E. Ebeler is a professor of chemistry at the
processes such as clarification and filtration, the impact of Department of Viticulture and Enology and the co-director of the Food
processing and storage was highlighted by our work. Knowing Safety and Measurement Facility at the University of California.
how different packaging types can change the elemental fin-
gerprint is of high importance for wine stability and shelf life. Direct correspondence to: hhopfer@ucdavis.edu ◾
Elemental fingerprints of high-priced food products such as
wine also provide insight into possible contamination sources,
for example, during processing, and how large these changes
are compared to differences because of geographical origin. For more information on this topic, please visit our
Similar approaches of elemental profiling have been suc- homepage at: www.spectroscopyonline.com
cessfully applied to distilled spirits, including whiskeys, tequi-
las, and gins, and can be used to gain a deeper understand-
ing of the processing impact on the elemental composition of
diverse foods and beverages. Ultra-Low Frequency Raman Spectroscopy
“Extend your Raman system into THz frequency range (5-200 cm-1)”
References
(1) International Organization of Vine and Wine (OIV), OIV-MA-C1-01: ϭϮϬϬϬ
Raman spectrum of several
ϭϬϬϬϬ ϯϮ ϰ
R2011 Maximum acceptable limits of various substances contained in layers of MoS2 fakes
/ŶƚĞŶƐŝƚǇ Ă Ƶ
ϯϮ ϰ
ဒϬϬϬ measured at 633 nm with
wine, 2011. ϲϬϬϬ BragGrate™ Notch flters and
(2) P. Pohl, TrAC Trends Anal. Chem. 26, 941–949 (2007). ϰϬϬϬ ϱ ϱ single stage spectrometer
ϮϬϬϬ ϭϯ ဒ ϭϯ ဒ (data courtesy of : P. H. Tan, State Key
(3) V.F. Taylor, H.P. Longerich, and J.D. Greenough, J. Agric. Food Chem. 51, Ϭ Laboratory of SL and Microstr.,
856–860 (2003). ϰϬ ϯϬ ϮϬ ϭϬ Ϭ ϭϬ ϮϬ ϯϬ ϰϬ Institute of Semiconductors,
ZĂŵĂŶ^ŚŝĨƚ Đŵ ϭ CAS, Beijing, P. R. China)
(4) E.C. Rossano, Z. Szilágyi, A. Malorni, and G. Pocsfalvi, J. Agric. Food
Chem. 55, 311–317 (2007).
(5) N. Jakubowski, E. Brandt, D. Stuewer, H.R. Eschnauer, and S. Görtges, BragGrate™ Bandpass and Notch Filters
Fresenius. J. Anal. Chem. 364, 424–428 (1999). Spectral and spatial laser line cleaning flters and ultra-narrow line notch
(6) H. Hopfer, J. Nelson, A.E. Mitchell, H. Heymann, and S.E. Ebeler, J. Anal. flters for low frequency Raman Spectroscopy
At. Spectrom. 28, 1288–1291 (2013).
(7) H. Hopfer, P.A. Buffon, S.E. Ebeler, and H. Heymann, J. Agric. Food
Chem. 61, 3320–3334 (2013).
(8) A.W. Boorn and R.F. Browner, Anal. Chem. 54, 1402–1410 (1982).
(9) R.F.J. Dams, J. Goossens, and L. Moens, Mikrochim. Acta 119, 277–286
(1995).
(10) J. Goossens, T. Smaele, L. Moens, and R. Dams, Fresenius. J. Anal. t'SFRVFODJFTCFMPXDN-1XJUITJOHMFTUBHFTQFDUSPNFUFS
488 nm 633 nm
Chem. 347, 119–125 (1993).
514 nm 785 nm t4UPLFTBOEBOUJ4UPLFT3BNBOCBOET
(11) J. Goossens, L. Moens, and R. Dams, Anal. Chim. Acta 293, 171–181 532 nm 1064 nm t6OMJNJUFEPQUJDBMMJGFUJNF
(1994). t$VTUPNXBWFMFOHUITJOSBOHFoON
(12) B. Tariba, Biol. Trace Elem. Res. 144, 143–156 (2011).
(13) R. Boulton, Am. J. Enol. Vitic. 52, 67–87 (2001). +1 (407) 542-7704
(14) C.M.R. Almeida and M.T.S.D. Vasconcelos, J. Agric. Food Chem. 51,
info@optigrate.com
w w w.optigrate.com
4788–4798 (2003).
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Sulfobutyl Ether-β-Cyclodextrin–
Assisted Fluorescence
Spectroscopy for Determination
of L-Amlodipine in Tablets
A spectrofluorometric method for the rapid and highly sensitive screening of
L-amlodipine was developed using sulfobutyl ether-β-cyclodextrin (SBE-β-CD)-
enhanced fluorescence detection. The method depends on measuring the native
fluorescence of L-amlodipine in water at 455 nm after excitation at 365 nm. Under
optimum reaction conditions, linear relationships with good correlation coefficients
(0.9998) were found between the fluorescence intensity and the concentrations of
L-amlodipine in the concentration range of 0.56–11.34 μg/mL with a limit of detection
0.17 μg/mL and limit of quantification of 0.55 μg/mL. The method was fully validated
and successfully applied for the determination of L-amlodipine in tablets with an aver-
age percentage recovery of 98.12–103.21%. Compared to reference methods, it has
merits of ease of accessibility, greater sensitivity, low-cost, and a broader range of
detection. Moreover, the inclusion interactions were examined by ultraviolet–visible
(UV–vis), fluorescence, and nuclear magnetic resonance (NMR) spectroscopy.
Lin Yang, Jiaqi Xie, Xiaoming Deng, Shenzhi Lai, and Xiaoming Chen
F rom 1980 to 2013, various types of cyclodextrins

became everyday commodities in separation sci-
ence as well as enabling additives for the enhance-
ment in sensitivity and selectivity of different analyti-
cal techniques (1). L -Amlodipine, or 2-[(2-aminoethoxy)
for its quantitative determination in pure, pharmaceuti-
cal dosage forms or biological f luids are necessary.
So far, high performance liquid chromatography
(HPLC) (4), gas chromatography (GC) with electron
capture detection (ECD) (5), capillary electrophoresis
methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-me- (CE) with UV detection (6), f low injection analysis (7),
thoxycarbonyl-6-methyl-1,4-dihydropyridine, is a cal- enzyme-linked immune sorbent assay (ELISA) (8), and
cium channel blocking agent of the dihydropyridine mass spectrometry (MS) (9,10) methods have been devel-
derivative, which is used in the treatment of hyperten- oped for the quantitative determination of L-amlodipine.
sion and angina (2). Moreover, it selectively inhibits the These methods offer the required sensitivity and selec-
arterial vascular smooth muscle cell proliferation, which tivity for the analysis of L -amlodipine, but problems as-
prevents the progressive narrowing of the arteries (3). sociated with high-analysis cost and long analysis times
Therefore, very sensitive and specific analytical methods cannot be ignored with respect to some of these methods.
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260
180
240
Relative fuorescence intensity

160
Relative fuorescence intensity
220
140
200
120
180
100
160
80
140
60
120
2 4 6 8 10 12
0 50 100 150 200 250
pH
Time (min)
Figure 1: Effect of time on the reaction of L-amlodipine with SBE-β-CD. Figure 2: Effect of pH on the reaction of L-amlodipine with SBE-β-CD.
In particular, the Fell group (11) has produced the earli- reaction with ninhydrin and phenylacetaldehyde.
est example of the resolution of amlodipine enantiomers In the present study, we extend the scope of Mahmoud’s
using a charged cyclodextrin additive in 52 min on a C8 research by avoiding tedious derivatization and using sul-
column, which possess a short analysis time for a spec- fobutyl ether-β-cyclodextrin (SBE-β-CD)-assisted spectro-
trof luorometric method. In 2008, A.M. Mahmoud and fluorometric analysis. This enabled the improvement in the
colleagues (12) reported the first example of spectrofluo- sensitivity and accuracy of luminescence spectroscopy and
rometric analysis of L -amlodipine by its condensation broadened the linear relationships with good correlation co-
Rigaku Corporation and its Global Subsidiaries

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was set at an excitation and emission

slit width of 5 nm. A thermostati-
cally controlled water bath (Schet-
1.6 1 zort) was used. The pH of the sam-
2 ples was measured using a Qph 70
1.4 pH meter (Shanghai REX). UV−vis
3
4 spectra were recorded using a Cary
1.2
5 50 Scan UV−vis spectrophotometer
Absorbance
1.0 6 (Agilent Technologies). NMR spectra

were recorded on a Bruker Avance
0.8 DMX-500 spectrometer. The size of
NMR tubes was 3 mm.
0.6
Chemicals and Reagents
0.4 All reagents were of analytical grade
and were used as received without
0.2
further purification. L -Amlodipine
0.0 besylate was purchased from Bei-
jing J&R Ti mes Technolog y Co.,
200 250 300 350 400 450 500 500 600 650 Ltd. SBE-β - CD was prov ided by
Wavelength (nm) Sha ndong X i nd a Fi ne Chem ic a l
Co., Ltd. The pH of separate por-
tions of the solution was adjusted
Figure 3: Upon increasing the concentration of SBE- β -CD, the absorption maximum is
to 2.0, 3.0, 5.0, 7.0, 9.0, and 11.0
systematically blue shifted from 366 to 360 nm.
before the addition of SBE-β-CD
at t he desi red concent rat ion, by
addition of sodium hydroxide and
phosphoric acid. The concentration
of SBE-β-CD was varied from zero
1000 to 2.0 × 10 -2 mol/L. A stock solution
1 of L -amlodipine (5 × 10 -3 mol/L)
2 was prepared. The available tablets
800 3 (Shihuida Pharmaceuticals (jilin)
Fluorescence intensity
4 Ltd.) used in the present investiga-

5 tion were labeled to contain 2.5 mg
600
6 L -amlodipine besylate per tablet.
Water was doubly distilled for the
preparation of aqueous solutions.
400
Preparation of Inclusion
200 Complex of L-Amlodipine
with SBE-β-CD
Accurately prepared 20-mL volumes
0 of L -amlodipine solution (5 × 10 -5
M) were t ra nsfer red i nto 50 -m L
350 400 450 500 500 600 conical f lasks. The pH was adjusted
to 3 by add i ng t he appropr i ate
Wavelength (nm)
a mount of NaH 2 PO 4 and H 3 PO 4 .
The same molar concentration of
Figure 4: Plot of the fluorescence spectra of L-amlodipine versus SBE-β-CD concentration. SBE-β-CD was prepared in distilled
water. Subsequently, 20 mL of SBE-
efficient (0.9998). Moreover, we inves- Experimental β -CD solut ion was added to t he
tigated the inclusion complex interac- Instrumentation L -amlodipine solution and stirred
tion of L-amlodipine and SBE-β-CD by An RF-5301 PC spectrof luorimeter with an electromagnetic stirrer. The
means of ultraviolet–visible (UV–vis), (Shi mad zu), w it h 1-cm matched mixture was continuously stirred
f luorescence, and nuclear magnetic quartz cells, was used for all mea- for 30 min at room temperature to
resonance (NMR) spectroscopy. surements. The spectrof luorimeter establish the optimum complexation
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equilibrium. The pH varied from 2

to 11, and all the solutions are trans-
parent. The prepared solutions were
placed in a 1-cm pathlength quartz
cuvette for obtaining f luorescence
spectra, then concentrated on a ro-
tary evaporator for recording the 1H
NMR spectrum. The 1H NMR spec-
tra were recorded at 400 MHz with
D 2 O as the solvent at 25 °C.
Tablet Solution
Figure 5: Formation of the inclusion complex between L-amlodipine and SBE-β-CD. The initial
Four tablets were weighed and finely
structures were optimized. Color labels: gray = carbon in L-amlodipine; white= hydrogen in
powdered. An accurately weighed
L-amlodipine; red= oxygen in L-amlodipine; blue = nitrogen in L-amlodipine; and green = chlorine
amount of pulverized tablets equiv-
in L-amlodipine. SBE-β-CD is shown with a annulus representation.
a lent to 10.0 mg of L -amlodipine
was transferred into a 100-mL cali-
brated f lask and dissolved in 100 absorption maximum is systemati- observed absorbance by further ad-
mL of water as stock solution. A cally blue shifted from 366 to 360 dition of SBE-β-CD. This behavior
1-mL volume of stock solution was n m a nd re su lt s i n a n en ha nc ed can be explained by a signif icant
pipetted into a 50-mL volumetric spectral response. The absorption and temporary change of the ana-
f lask and diluted to the mark with spectra of L -amlodipine undergo a lyte microenvironment (from aque-
the same solvent according to the slight blue shift, showing a change ous hydrophilic to t he lipophi lic
method mentioned above. in absorption maxima even in the phase) in the SBE-β-CD cavity.
presence of the highest concentra- In water, the relatively lipophilic
Results and Discussion tion of SBE-β-CD used (2 × 10 -2 na noc av it ies of SBE-β - CD of fer
Optimization of Reaction Conditions mol/L). There is no change in the such a local microenvironment for
Effects of Time on the Reaction
of L-Amlodipine with SBE-β-CD
The results obtained from optimiz-
ing the reaction time indicated that
the maximum f luorescence intensity
was attained after 30 min. As seen
in Figure 1, longer reaction times
led to a reduction in the f luores-
cence intensity. Therefore, all sub- The MicroNIR™ Spectrometer:
sequent experiments were carried
out at room temperature for 30 min. Ultra-Compact, Lightweight,
and Cost-Efective
Effects of pH with SBE-β-CD Medium
For investigating the effect of pH, A feld, at-line, and on-line
the complexation reaction was per-
formed at different pH values (2.00–
near-infrared analyzer
11.00). The results indicated that the
fluorescence intensity was pH depen- See the MicroNIR spectrometer at
dent, as shown in Figure 2. The opti-
mum pH for maximum f luorescence booth #71 in the South Hall
intensity was found to be 3.0. and visit www.jdsu.com/go/micronir
Effect of SBE-β-Cyclodextrin
The UV–vis absorption spectra of
L -amlodipine at different concen-
trations of SBE-β-CD are show n
in Figure 3. The absorption peaks
of L -amlodipine at pH 3.0 appear
at 366 n m. Upon i ncreasi ng t he
concent rat ion of SBE-β - CD, t he
magenta
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yellow
of the initial structure and calcu-

lation of t he complex’s structure
energ y (-7554.2520640 Har trees)
indicates it is fairly stable (Figure
Guest 5). This result is clearly consistent
with the fact that SBE-β-CD forms a
stable 1:1 complex with L -amlodip-
ine in water, and indicates that the
CH 2 NH 3 + group of L -amlodipine is
trapped and retained in the cavity
of SBE-β-CD.
Complex
NMR Analysis of the
Interactions Between L -Amlodipine
and the Anionic SBE-β-CD
SBE- β -CD Figure 6 shows the changes in the
1H NMR signals of L -amlodipine in-
duced by the addition of SBE-β-CD

in D 2 O at 25 °C. Upon the addition
of SBE-β-CD, significant chemical
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 shift changes of the protons on L -
δ (ppm) amlodipine were noted. The signal
corresponding to L -amlodipine at
Figure 6: 1H NMR spectra (400 MHz): (upper) L-amlodipine (guest); (lower) SBE- β -CD δ = 6.15 and δ = 4.50 ppm disap-
(host); (middle) 1:1 Complex of L-amlodipine–SBE- β -CD. 1H NMR spectral changes peared, whereas the resonance sig-
observed in D 2 O at 25 °C. Red circles denote the signals associated with L-amlodipine at nals associated with SBE-β-CD all
δ = 6.15 and δ = 4.50 ppm disappeared. shifted downfield dramatically and
broadened. Slight broadening oc-
Table I: Quantitative parameters for the mentioned spectrofluorometric methods for analysis curred because of the complexation
of L-amlodipine dynamics (Figure 6). Shielding ef-
Method R2 LOD (μg/mL) LOQ (μg/mL) Linearity (µg/mL) fects exist between SBE-β-CD (the
SBE-β-CD 0.9998 0.17 0.55 0.56–11.34 host) a nd t he L -a m lod ipi ne (t he
Ninhydrin 0.9985 0.091 0.304 0.35–1.8
guest). These phenomena provided
strong evidence for interactions be-
tween SBE-β-CD and L -amlodipine.
L -amlodipine that it results in the The Stoichiometry Between L-Amlo-
usef u l en ha ncement of t he f luo- dipine and the Anionic SBE-β-CD Validation of the Proposed Methods
rescence signals of the complexed Using the methods of Likussar and Linearity and Sensitivity
analy te. The f luorescence spectra Bolt z (13), cont i nuous-va r iat ion Under the specified optimum reac-
cha nges of L -a m lod ipine plot ted plots were generated. In the char- tion conditions, calibration curves
against the SBE-β-CD concentra- acteristic triangu lar continuous- for L -a m lod ipi ne w it h d i f ferent
tion (Figure 4) illustrate two effects: variation plots, the function used analytical reagents used were con-
First, the f luorescence spectrum is was (AL)/([AL]+[CD]) on t he or- structed by measuring a series of
blue shif ted from 455 to 442 nm. dinate, against (CD)/([AL]+[CD]) eight concentrations of the standard
Second, the f luorescence intensity on the abscissa. This indicates that solutions of L -amlodipine. All mea-
of L -amlodipine initially decreased, the continuous-variation plot has surements were carried out using six
then subsequently increased with an a maximum corresponding to the replicate measurements (n = 6). The
increase in the value of SBE-β-CD L -amlodipine–anionic SBE-β-CD assays were carried out according to
concentration, which is consistent molar fraction in solution of 0.5:0.5 the general procedures previously
w it h t he for mat ion of i nclu sion and further indicates a stoichiome- established. In all cases, standard
complexes between L -amlodipine try of 1:1 for the complex between L - curves were linear with acceptable
a nd SBE - β - CD. W hen t he SBE - amlodipine and anionic SBE-β-CD intercepts and very good correlation
β-CD concentration was 2 × 10 -2 is the predominant molecular spe- coefficients (0.9998) in the general
mol/L, the f luorescence maxima can cies in solution (14). Moreover, using concentration range of 0.56–11.34
be attained. Thus, a concentration the software tool DMol3 found in μg/mL (Table I) .
of 2 × 10 -2 mol/L SBE-β-CD was se- the Materials Studio software pack- The limit of detection (LOD) was
lected for subsequent experiments. age (Accelrys), both optimization defined as the concentration of drug
magenta
cyan
yellow
giving a signal-to-noise ratio of 3:1; References

while the lower limit of quantifica- (1) L. Szente and J. Szemán, Anal. Chem. 85,
tion (LOQ) was determined using 8024–8030 (2013).
the formula: (2) B. Suchanova, R. Kostiainen, and R.A. Ketola,
Eur. J. Pharm. Sci. 33, 91–99 (2008).
High Performance
LOQ = 10 × (SDa)/b [1] (3) Y.M. Lai, N. Fukuda, J.Z. Su, R. Suzuki, Y.
Ikeda, H. Takagi, Y. Tahira, and K. Kanmat- Lasers by Cobolt.
where SDa is the standard deviation suse, Hypertens. Res. 25, 109–115 (2002).
of the intercept, and b is the slope. (4) A.R. Tengli, B.M. Gurupadayya, and N. Soni,
From the results of the calculation, Inter. J. Chem. Anal. Sci. 4, 33–38 (2013).
we obtained an LOD = 0.17 μg/mL, (5) F. Scharpf, K.D. Riedel, H. Laufen, and M. Lei-
while the LOQ = 0.55 μg/mL. told, J. Chromatogr. B. 655, 225–233 (1994).
(6) P. Mikǔs , K. Maráková, J. Marák, I. Nemec, I.
Precision Valášková, and E. Havránek, J. Chromatogr. B.
The precision of the method was es- 875, 266–272 (2008).
timated by measuring six replicate (7) G. Altiokka and M. Altiokka, Pharmazie. 57,
samples of L -amlodipine. The assays 500 (2002).
provided satisfactory results, where (8) K. Matalka, T. El-Thaher, M. Saleem, T. Arafat,
t he rel at ive s t a nd a rd de v i at ion A. Jehanli, and A. Badwan, J. Clin. Lab. Anal.
(RSD) was 0.73%, less than 2%. This 15, 47–53 (2001).
level of precision of the proposed (9) K. Sarkar, D. Ghosh, A. Das, P.S. Selvan, K.V. ;QWTHKTUVEJQKEG
method was adequate for the qual- Gowda,U. Mandal, A. Bose, S. Agarwal, U.
ity control analysis of L -amlodipine Bhaumik, and T.K. Pal, J. Chromatogr. B. 873, HQT4COCP
in its pharmaceutical dosage forms. 77–85 (2008).
(10) J.Z. Shentu, L. Z. Fu, H.L. Zhou, X.J. Hu, J. Liu,
Analysis of Pharmaceutical J.C. Chen, and G.L. Wu, J. Pharm. Biomed. %9&255NCUGTU
Dosage Forms Anal. 70, 614–618 (2012).
The validity of the proposed method (11) P.K. Owens, A.F. Fell, M.W. Coleman, and J.C. 355 – 1064 nm
for the determination of L-amlodipine Berridge, Chirality 8, 466–476 (1996). Extreme spectral purity
in pharmaceutical preparations was (12) H.M. Abdel-Wadood, N.A. Mohamed, and
• 'ZEGNNGPVYCXGNGPIJV
tested by application of the standard A.M. Mahmoud, Spectrochim. Acta, Part A.
addition technique. The results ob- 70, 564–570 (2008).
UVCDKNKV[
tained were reproducible and the (13) W. Likussar and D.F. Boltz, Anal. Chem. 43, 7NVTCTQDWUV
mean recoveries were in the range of 1265–1272 (1971).
98.12–103.21%. (14) P.K. Owens and A.F. Fell, J. Chromatogr. A.

797, 187–195 (1998).

Conclusion
The present study describes a vali- Lin Yang, Jiaqi Xie,
dated spectrof luorometric method Xiaoming Deng, Shenzhi

for the analysis of L -amlodipine in Lai, and Xiaoming Chen ə
tablets. Because L -amlodipine forms are with the Key Laborator y of
a 1:1 complex with SBE-β-CD, the Environment-Friendly Chemistr y and
method has merits of being simple, Application in Ministr y of Education at
rapid, accurate, and reliable for the the College of Chemistr y at Xiangtan %XLOWZLWK+7&XUHWHFKQRORJ\
determination of L-amlodipine in tab- University in Xiangtan, China. ZKLFKKDVHQDEOHG&REROWWR
lets. The method also has great value VXSSO\XOWUDUREXVW6/0'366
for the quality control analysis of L - Direct correspondence to:
ODVHUVZLWKSURYHQUHOLDELOLW\IRU
amlodipine because of its improved 352180014@qq.com ◾
simplicity and sensitivity. RYHUDGHFDGH
Acknowledgments
This work was supported by the Na-
tional Natural Science Foundation For more information on this topic,
of China (21305118), a nd Huna n please visit our homepage at: www.cobolt.se
Prov incia l Science & Technolog y www.spectroscopyonline.com
Department (2013SK2021). All au- Cobolt AB, Sweden • Cobolt Inc, USA
thors express their sincere thanks.
magenta
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Good Practices to Control

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Contamination control in elemental analyses is very important because contamination Anastasia Khvataeva
can seriously undermine analytical processes and compromise the data. Selecting water WW Application Development
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blanks, zero interferences, and repeatable elemental data. Poor practices in ultrapure Merck Millipore, France
water handling along the analytical process as well as neglecting some contamination
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Molecular Spectroscopy Workbench

Y ou were probably first introduced to rotational

infrared absorption spectroscopy of gases. If so, that Carbonated Beverages

Table I: Assignment of Raman bands in

2ν2 13C16O 1369.3

2ν21 12C16O 1408.8

the OH stretching bands narrow

cm-1, which can be attributed to WITec Headquarters

ing modes are also affected, but to

Intensity (arbitrary units)

2600 2800 3000 3200 3400 3600 3800

Figure 4: Raman spectra of liquid- and vapor-phase methanol.

Intensity (arbitrary units)

2000 2200 2400 2600 2800 3000 3200

FWHM: 1.1 cm–1

960 980 1000 1020 1040

Figure 6: Raman spectra of liquid- and vapor-phase benzene.

Figure 7: Raman spectrum of oxygen in air. Note the rotational side -

rowing of the FWHM to 1.1 cm -1.

O S Studying the Raman spectra

80 O Branch: ν vib – ν rot , Δ J = -2 [1]

Q Branch: ν vib , Δ J = 0 [2]

selection rule of Δ J = ±1. An additional consideration interactions. Finally, vibrational-rotational Raman

intensity of the sidebands as predicted by nuclear spin

I n the May 2014 issue of Pharmacopeial Forum, the U.S.

What is required is a discussion

Howard Mark and Jerome Workman, Jr.

T his column is the next continuation of our dis-

Table I from part X (11), as we This nonequivalency has nothing to do with

Handheld Raman for

^WϮϬϭϰ hs sŝƐŝďůĞ E/Z Stephen A. Brown