UNIT II B: GRAVIMETRIC ANALYSIS

GRAVIMETRY
 Laws and Theories of Chemistry related to Gravimetric Analysis
 Types of Gravimetric Analysis
 Calculations Involved

OBJECTIVES:
 Be aware of the importance or purpose for each determination, the principle and procedure involved.
 Enumerate the methods of separating the active constituent from the sample to be assayed
gravimetrically.
 Calculate the percentage purity or percentage content of substances being analyzed.
LAWS AND THEORIES
 Most of the reactions involved in quantitative analysis are of the reversible type.
 Three general conditions tend to prevent reversal and lead to completion of a reaction:
1. The formation of an insoluble gas
2. The formation of a sparingly soluble solid
3. The formation of very slightly ionized molecules
Law of Mass Action
1. It states that, “At constant temperature, the rate of a chemical reaction is directly proportional to the
active mass of the reactant present at that time. If more than one reactant takes part in the reaction
then the rate of the reaction is proportional to the product of the active masses of the reactants.”
Solubility Product Principle
 It is an application of the law of mass action to equilibria that generalizes the behavior of difficulty
soluble salts in their saturated solutions.
 The principle may be stated as follows: The product of the concentration of the constituent ions in a
saturated solution of a difficulty soluble salt for any given temperature is practically a constant, each
concentration being raised to a power equal to the relative number of ions supplied by one molecule of
the salt upon dissociating.
Common-Ion Effect
 It is responsible for the reduction in the solubility of an ionic precipitate when a soluble compound
combining one of the ions of the precipitate is added to the solution in equilibrium with the precipitate.
 Defined as the suppression of the degree of dissociation of a weak electrolyte containing a common
ion.
Gravimetric methods (Gravimetry)
 are quantitative methods that are based on determining the mass of a pure compound to which the
analyte is chemically related.
CLASSIFICATION OF GRAVIMETRIC METHODS
Precipitation Gravimetry
 the analyte is separated from a solution of the sample as a precipitate and is converted to a compound
of known composition that can be weighed.
Volatilization Gravimetry
 the analyte is separated from other constituents of a sample by conversion to a gas of known chemical
composition. The weight of this gas then serves as a measure of the analyte concentration.
Electrogravimetry
 the analyte is separated by deposition on an electrode by an electrical current. The mass of this product
then provides a measure of the analyte concentration.
PROPERTIES OF GRAVIMETRIC ANALYSIS
 Traditional Method
 Cheap, easily available apparatus, simple to carry out.
 Slow, especially when accurate results are required.
 Wide range of sample concentrations (ng - kg).
 No calibration required (except for the balance).
 Accurate.
PRECIPITATION GRAVIMETRY
 In precipitation gravimetry, the analyte is converted to a sparingly soluble precipitate.
  This precipitate is then filtered, washed free of impurities, converted to a product of known composition
by suitable heat treatment, and weighed.
PROCEDURE FOR PRECIPITATION GRAVIMETRY
 Preparation of Solution
 Precipitation
 Digestion - is a process in which a precipitate is heated for an hour or more in the solution from which it
was formed
 Filtration
 Washing
 Drying or Igniting
 Weighing
 Calculation
PROPERTIES OF GOOD PRECIPITATES
 Easily filtered and washed free of contaminants
 Of sufficiently low solubility that no significant loss of the analyte occurs during filtration and washing
 Unreactive with constituents of the atmosphere
 Of known chemical composition after it is dried or, if necessary, ignited.
PARTICLE SIZE OF SOLIDS
COLLOIDAL SUSPENSION
 whose tiny particles are invisible to the naked eye (10-7 - 10-4 cm in diameter).
 Colloidal particles show no tendency to settle from solution
 not easily filtered.
CRYSTALLINE SUSPENSION
 particles with dimensions on the order of tenths of a millimeter or greater.
 The temporary dispersion of such particles of a tend to settle spontaneously,
 easily filtered.
PRECIPITATION MECHANISM
 Induction period
 Nucleation
 Particle growth to form larger crystals
 Adsorption
 Electrostatic
IMPURITIES IN PRECIPITATES
 Precipitates tend to carry down from the solution other constituents that are normally soluble, causing
the precipitate to become contaminated. This process is called coprecipitation.
 In other words, coprecipitation is a phenomenon in which otherwise soluble compounds are removed
from solution during precipitate formation.
TYPES OF COPRECIPITATION
 Surface adsorption
 Mixed-crystal formation
 Occlusion
 Mechanical entrapment
SURFACE ADSORPTION
 Adsorption is a common source of coprecipitation and is likely to cause significant contamination of
precipitates with large specific surface areas, that is, coagulated colloids.
 The net effect of surface adsorption is therefore the carrying down of an otherwise soluble compound
as a surface contaminant.
MIXED-CRYSTAL FORMATION
 Mixed-crystal formation, one of the ions in the crystal lattice of a solid is replaced by an ion of another
element.
 For this exchange to occur, it is necessary that the two ions have the same charge and that their sizes
differ by no more than about 5%.
 This problem occurs with both colloidal suspensions and crystalline precipitates.
OCCLUSION
 Occlusion is a type of coprecipitation in which a compound is trapped within a pocket formed during
rapid crystal growth, material that is not part of the crystal structure is trapped within a crystal.
 Occluded impurities are difficult to remove. Reprecipitation that go on at the elevated temperature of
digestion open up the pockets and allow the impurities to escape into the solution.
MECHANICAL ENTRAPMENT
 Mechanical entrapment occurs when crystals lie close together during growth.
 Here, several crystals grow together and in so doing trap a portion of the solution in a tiny pocket.
TYPES OF PRECIPITATING AGENT
 Inorganic Precipitating Agents
 These reagents typically form slightly soluble salts or hydrous oxides with the analyte.
 Reducing Agents
 This type of reagents convert an analyte to its elemental form for weighing.
 Organic Precipitating Agents
 Two types of organic reagents. One forms slightly soluble non-ionic products called coordination
compounds; the other forms products in which the bonding between the inorganic species and the
reagent is largely ionic.
 Organic Precipitating Agents
 Organic precipitating agents have the advantages of:
1. Some of organic precipitating agents are very selective, and others are very broad in the number of
elements they will precipitate.
2. Giving precipitates with very low solubility in water.
3. Give a favorable gravimetric factor.
CALCULATIONS IN GRAVIMETRY
 Find moles of precipitate

 Find moles of sought substance

 Find weight of sought substance

  Calculate the percentage of the sample that is the sought substance

EXAMPLES

 A 0.4960 g sample of a CaCO3 is dissolved in an acidic solution. The calcium is precipitated as

CaC2O4.H2O and the dry precipitate is found to weigh 0.6186 g. What is the percentage of CaO in
the sample?

0.2374 g

 0.4960 g sample of a CaCO3 is dissolved in an acidic solution. The calcium is precipitated as

CaC2O4.H2O and the dry precipitate is found to weigh 0.6186 g. What is the percentage of CaO in
the sample?

=47.86%

 An ore is analyzed for the manganese content by converting the manganese to Mn3O4 and weighing it.
If a 1.52 g sample yields Mn3O4 weighing 0.126 g, what would be the percent Mn2O3 in the sample? The
percent Mn?

Solution:% of Mn2O3

Solution: % Mn
UNIT III. SPECIAL METHODS OF ANALYSIS

OBJECTIVES:
 State the importance or purpose for each determination, the principle and procedure involved.
 Compute the ash and moisture content of drugs and the amount of extractives and crude fiber of crude
drugs.
 Acquire the skills of determining the different constants of fats and related substances.
 Understand the importance of knowing the quality/purity of fatty or oily substances and other similar
substances.
 Determine the components and properties of volatile oils.
 Analyze the volatile oil content of crude drugs and spirits.
 Be familiar with the definition and properties of alkaloids.
 State the principles and procedures involved in the assay of alkaloids.
 Calculate the alkaloidal content of crude drug and dosage forms.
ANALYSIS OF CRUDE DRUGS
CRUDE DRUGS
 A crude drug is any naturally occurring, unrefined substance derived from organic or inorganic sources
such as plant, animal, bacteria, organs or whole organisms intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease in man or other animals.
SPECIAL METHODS USED IN PHARMACEUTICAL ANALYSIS
Classification:
 Chemical methods, such as those employed in the determination of ash, moisture, crude fiber,
extractive obtained with different solvents, the estimation of alkaloidal content, etc.
 Biological methods, or those in which the effects of drugs upon microbes, animals or animal tissues are
measured and which are employed in absence of satisfactory chemical methods for standardization.
Ash Determination
LIMIT ON ASH VALUE
 Ash Value (Total Ash)
 Acid-Insoluble Ash
 Sulfated Ash
 Water-Soluble Ash
ASH VALUE (TOTAL ASH)
 Ash value normally designates the presence of inorganic salts e.g., calcium oxalate found naturally in
the drug, as well as inorganic matter derived from external sources.
 Incineration
Substances with Ash Limits
Pharmaceutical Substance Prescribed Limit (%)
Aloin NMT 0.5
Catechu NMT 0.8
Sumatra Benzoin NMT 2.0
Indian Squill NMT 6.0
Sterculia NMT 7.0
ACID INSOLUBLE ASH
 Acid – Hydrochloric acid (HCl)
 NOTE: Acid-insoluble ash value of a crude drug is always less than total ash value of the same drug.
Substances with Ash Limits
Pharmaceutical Substance Prescribed Limit (%)
Aniseed NMT 2.5
Coriander NMT 1.5
Rhubarb NMT 1.0
Senna leaf NMT 4.0
Digitalis leaf NMT 5.0
SULFATED ASH
  The sulfated ash test uses a procedure to measure the amount of residual substance not volatilized
from a sample when the sample is ignited in the presence of sulfuric acid.
 The test is usually used for determining the content of inorganic impurities in an organic substance.
Substances with Ash Limits
Pharmaceutical Substance Prescribed Limit (%)
Substances of Natural Origin
Wood alcohol NMT 0.15
Wool fat NMT 0.15
Activated charcoal NMT 5.0
Organic Substances
Cephalexin NMT 0.20
Griseofulvin NMT 0.10
Saccharin NMT 0.20
Inorganic Substances
Ammonium chloride NMT 0.10
Hydroxyurea NMT 0.20

WATER-SOLUBLE ASH
 Water-soluble ash is specifically useful in detecting such samples which have been extracted with
water.
 A typical example of an official drug is that of ‘Ginger’, the water-soluble ash of which is found to be not
more than 6.0%.
% ASH VALUE

% ash = weight of residue x 100

weight of sample
COMPUTATION:
Weight of empty dish = 53.8 g
Weight of cinchona bark = 2g
Weight of the dish + ash (after complete incineration) = 53.87 g
A) Compute for the Total Ash (% ash value)
B) Does the result conforms with the standard ash value of cinchona bark? Cinchona bark = NMT 4
Solution:

Moisture Determination

TECHNIQUES FOR MEASURING MOISTURE CONTENT

 Thermogravimetric
 Chemical
 Spectroscopic
THERMOGRAVIMETRIC MOISTURE DETERMINATION
 Thermogravimetric moisture analysis calculates moisture content based on loss of weight on
drying. Disadvantage: heat may cause decomposition of the samples
 Microwave ovens (professional, not household) can accommodate larger sample sizes than a moisture
balance but do not offer the high degree of temperature control found with moisture balances. 
Microwave drying is not suitable for samples with water content less than 2%.
 Drying ovens use circulating hot air, sometimes under vacuum, to establish reference moisture
content. 
  Phosphorous pentoxide is a powerful and dangerous desiccant used as a drying agent for materials
with which it does not react. 
 The distillation method is favorably priced but requires solvents that can create disposal problems. 
CHEMICAL MOISTURE DETERMINATION
 Karl Fischer titration
 Calcium carbide method
KARL FISCHER METHOD FOR DETERMINATION OF WATER
 Karl Fischer reagent is composed of iodine, sulfur dioxide, pyridine and methanol.
 Titer of the Karl Fischer reagent stands at 3.5 mg of water per milliliter of reagent.
 Used in
a. Prednisolone sodium phosphate
b. Rifamycin sodium
c. Sodium methyl hydroxybenzoate
d. Triamcinolone acetonide
Formula:

% Water = V (KF) x Water EF x 100

Wt. of sample (mg)

V (KF) – volume of Karl Fischer reagent (mL)

EF – Equivalence factor of water

SPECTROSCOPIC MOISTURE ANALYSIS

 Infrared (surface moisture)
 Microwave (total moisture)
 Nuclear magnetic resonance (NMR) spectroscopy

% MOISTURE

Weight of moisture x 100

Weight of sample

COMPUTATION:
1.
Weight of empty crucible = 55.82 g
Weight of sample = 0.5 g
Weight of the dish + sample (after drying) =55.95 g
Compute for the % moisture:

Solution:

2.
Weight of sample = 0.3 g
Volume of KF reagent used = 25 mL
Compute for the % water content using KF method
Solution:

Determination of Extractives
METHODS
 Dilute ethanol-soluble extract – dilute ethanol, maceration
  Water-soluble extract – water
 Diethyl ether-soluble extract – diethyl ether, reflux condenser
SOXHLET EXTRACTION APPARATUS
 Generally used for extraction with volatile solvents where small quantities of are to be extracted.
HEXANE-SOLUBLE EXTRACTIVES
 Hexane is the best solvent for fats and fatty oils hence, this method provides an index of the amount of
fat in a sample and amount of seeds in some plant materials.

% EXTRACT CONTENT
Weight of extract x 100
Weight of sample
COMPUTATION:
1. What is the percent hexane extractive if 27.5820 g of a crude yields a residue of 0.9155 g of the
extractive?
Solution:

2. A 2.3479g sample of Aloe was assayed for its glycosidic content and yielded 1.4897g extractive after
evaporation and drying to constant weight. What is the percent of water-soluble extractive?
Solution:

Determination of Crude Fiber

CRUDE FIBER CONTENT
 The crude fiber content is the residue that remains undissolved after successive treatment with boiling
alkali and acid.
 Sulfuric acid and Sodium hydroxide
 Ash obtained is subtracted from the residue obtained after treatment with the base.

% CRUDE FIBER CONTENT

Weight of crude fiber x 100
Weight of sample

COMPUTATION:
1. The ether-insoluble residue of a 7.6100 g sample of cocoa is 2.7314 g and this was assayed for crude
fiber content. What is the percent crude fiber content of this cocoa powder sample if after treatment with
boiling H2SO4and NaOH, a total ash of 1.6489g was obtained from a 1.8382g of residue left after acid
and alkali treatment?
Solution:

CONSTANTS OF FATS, OILS, WAXES, BALSAMS AND RESINS

ANALYSIS OF FATTY SUBSTANCES

  Such methods usually consist of the determination of physical and chemical properties or values known
as constants.
 When taken in conjunction with organoleptic tests and special ID tests, such methods form the basis
upon which the purity and quality of fat samples are judged.

 Physical constants such as specific gravity, solubility, melting point, congealing point, refractive index
and optical activity determinations are discussed in the official compendia.
 Some samples employ tests for moisture and non-fatty tissue residues and are labeled under the
heading “Water and Sediment Content”. This is of importance in fatty oils especially of animal origin.

Acid Value
 Number in mg of potassium hydroxide necessary to neutralize the free fatty acids in 1g of oil, fat, wax,
resin, balsam, or similar organic substance of complex composition.
 May also be expressed as the number in mL of 0.1N NaOH required to neutralize the free fatty acids in
10g of fat sample.
 Procedure carried out by dissolving the sample in ether solution and titration with standard alkali
solution.
 Balsams and resins are dissolved in ether solution since the coloring matter is dissolved in the ethereal
layer.
 Solid fats and waxes are melted on a water bath and titrated while hot.
 A high acid value, compared to the maximum official requirement or maximum limit, indicate extensive
hydrolytic decomposition of the fat sample.
 It does not necessarily indicate rancidity since this is due to action of air or bacteria.
 A low acid value, compared to the minimum official requirement or minimum limit indicates adulteration
and an inferior quality since fat samples inherently contain free fatty acids.
 In titration of fatty substances:
 The sample should be clear.
 The sample should be introduced by a dropper or a Pasteur pipet.
 It is necessary to shake the mixture thoroughly after addition of each portion of alkali to secure
complete extraction of the fatty acids to be neutralized from the oily layer.

Formula:

V of KOH x N x 56 = mg of KOH/g
Weight of sample

COMPUTATION:
1. If a 2g sample of cod-liver oil required 4.5mL of 0.02N KOH in the titration of its free fatty acids, what is
its acid value?
Solution:

Saponification Value
 Number in mg of potassium hydroxide required to neutralize the free fatty acids and saponify the esters
contained in 1 g of fat, fatty oil or volatile oil, wax, resin, balsam or other substance of similar
composition.
  Quantifies the glycerides of acids and detects the presence of unsaponifiable matter present as
adulterant.
 The sample is treated with an excess of 0.5N KOH and heated in a flask with an air condenser, with
constant shaking to accelerate saponification.
 KOH is used in order to solubilize the sample and the saponification products.
 The excess is back titrated with 0.5N HCl and a blank determination is performed.
 H2SO4 must not be used as a substitute since K2SO4 is insoluble.

Formula:

56 (B – S) x N of HCl
Weight of sample (g)
B – mL of HCl required by blank
S – mL of HCl required by sample

COMPUTATION:
1. What is the saponification value of cottonseed oil if a 1.532g sample treated with 25mL of 0.5N KOH
required 15.70mL of 0.51N HCl for the residual titration? The blank determination required 26mL of the
standard acid.
Solution:

Ester Value

 Number in mg of potassium hydroxide required to saponify the esters in 1g of fat, fatty oil or volatile oil,
wax, balsam, resin or similar substance.
 In samples that contain free fatty acids, ester value is equal to the difference between the saponification
value and acid value.
 In samples that don’t contain free fatty acids, ester value is equal to the saponification value.
 Important in the analysis of waxes to indicate the presence of adulterants especially paraffin.
 Addition of acid value to the ester value will give the saponification value.

COMPUTATION:
1. If a sample of beeswax is found to have an acid number of 20.4 and a saponification value of 89.8,
what is the ester value?
Formula:
EV = SV - AV

Solution:

Unsaponifiable Matter
 Substances present in oils or fats that are not saponified by alkali hydroxides but are soluble in
ordinary fat solvents.
 Usually added as an adulterant to fat samples.
 Normally are dissolved in soap solution after saponification with KOH, but floats on top of the
reaction mixture if large amounts are present.
 Indicates quality and purity.
 Method conducted by treatment of the sample with KOH with subsequent evaporation of the
residue that remains is dissolved in water and the unsaponifiable matter extracted by ether.

Iodine Value
 Number in g of iodine absorbed under specified conditions by 100g of oil, fat, wax or other
substance.
 Quantifies the unsaturated fatty acids, both in the free and combined form.
 It serves to characterize oils if they are pure or admixtures.
Range of Iodine Values: (g/100g)
 >120 –Drying Oils e.g. Linseed and Cod-Liver Oil
 100-120 –Semi-drying Oils e.g. Cottonseed and Sesame oil
 < 100 –Non-drying Oils e.g. Olive and Almond Oil
 Animal fat usually have iodine values below 90
 In conjunction with saponification value, adulteration can be detected as well as the nature of
the adulterant.
 The sample is dissolved in carbon tetrachloride and treated with Iodine
Monochloride/Iodochloride T.S. (ICl) in excess inside a glass-stoppered flask to prevent loss
and protected from light to prevent other side reactions from occurring.
 If the solution is no longer yellow after such procedure, the test is repeated with a smaller
amount of sample.
 The excess ICl is treated with KI T.S. to liberate Iodine.
 An excess of KI is added to ensure complete removal of free chlorine and prevent precipitation
of iodine in aqueous solution.
 The liberated I2 is titrated with standard Na2S2O3.
 A blank determination is carried out to correct for errors and to make it unnecessary to
determine the N of Iodochloride.

Formula:

(B – S) x N of Na2SO3 x 0.127 g/mEq x 100

Weight of sample (g)
COMPUTATION:
1. Determine the iodine value of a sample of olive oil weighing 0.2100g if 24.15mL and 12mL of
0.1100N sodium thiosulfate solution are required for the blank and residual titrations
respectively.
Solution: