mACLEOii)~

MACLEODS PHARMACEUTICALS LIMITED

11111I1111111111111111111111

Andheri (East), MUMBAI

TELMISARTAN TABLETS

ANAL YTICAL METHOD EQUIVALENCY

AND JUSTIFICATION REPORT FOR ASSAY

3.2.P.5.3

Page 338

Ii1ACLEOi)~

MACLEODS PHARMACEUTICALS LIMITED

I1I1III1I1III111111111111111

Andheri (East), MUMBAI

TELMISARTAN TABLETS

ANALYTICAL METHOD EQUIVALENCY

AND JUSTIFICATION REPORT FOR ASSAY OF
TELMISARTAN
REPORT NO.: MEJRlDP/A/2011/00S/00
(REFERENCE PROTOCOL NO.: MEJPIDP/A/2011100S/OO)

Prepared by:
Mr. Rajiv Bhandhari
Research Associate - ARD

Date:

Checked by:

t'e1 r fl--I ~l

Mr. Sanjay Patel

Jr. Research Scientist - ARD

&L

Reviewed By: _ _ _ _ _ _ __

Date:

0 f:. \ \'L\ II

Date:

pt. 12-' ~/,

Mr. Vibhakar Chaurasia

Team Leader- II - ARD

Approved By:

~r
Mr. Shridhar Koparkar VP - ARD

Approved By:

~R~D--::ll::::::O===~_ - - Mr. Rakesh Chaurasia GM - RAD

Date:

3.2.P.5.3

Page 339

IiIACLEOD~

1111111111I11111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDP/A/2011100S/OO

Page 1 of25

INDEX

Sr. No.

Description

Objective and Scope

Method Equivalency Parameters performed

Materials, Chemicals and Reagents,

Instruments/Equipments and Column used for Method
Equivalency

Analytical Methodology

Results and observation

16

Summary of the Report

25

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3.2.P.5.3

Page 340

mACLEOD~

1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDPI A12011100S/OO

Page 2 of25

1. OBJECTIVE AND SCOPE

Objective
The objective of this report is the method comparison between validated in house method and
Compendial method (USP 34 NF 29) for Assay. In house assay, method was developed and
validated for Telmisartan Tablets 80mg. (Refer Report No. AVRlDP/023/00/HPLC).

Scope
The In house validated analytical method for Assay is same for all the strengths of Telmisartan
Tablets i.e. 20 mg, 40 mg and 80 mg. Hence under the method equivalency under the method
equivalency of in house method against USP method, Specificity and Repeatability study was
carried out on higher strength i.e. Telmisartan Tablets 80 mg and results will be compared. The
Method equivalency data is applicable for Telmisartan Tablets 20 mg and 40 mg also.

Analytical method reference:

Sr.
No.

Reference
STP No.

Product name

Reference
SPC No.

In house method

Telmisartan tablets 20 mg

Telmisartan tablets 40 mg

Telmisartan tablets 80 mg

SPCIFP /1S 77/01

STP/FP/lS77/01

SPCIFPIlS78/01
SPCIFP/1S79/0 1

Compendial method

USP 34 NF 29

Telmisartan tablets

STP: Standard Test Procedure, SPC: specification

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3.2.P.5.3

Page 341

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m4CLEOi)~

1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDP/A/2011100S/OO

Page 3 of25

2. METHOD EQUIVALENCY PERFORMED

For In house Method
Sr.No

01

Method Equivalency parameters

Performed

Specificity

A) Interference

02

03

Precision
System precision

Repeatability

System suitability

For USP Method

Sr.No

01

Method Equivalency parameters

Performed

Specificity

A) Interference

02

03

Precision
System precision

Repeatability

...J

System suitability

-..J

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mACLEOD~

1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDP /Al20111008/00

Page 4 of25

LIST OF ANNEXURES
Annexure
No.

Annexure

Blank Chromatogram (In House Method)

Resolution Chromatogram (In House Method)

Standard Chromatogram (In House Method)

Sample Chromatogram (In House Method)

Blank Chromatogram (Assay / RS USP Method)

Placebo Chromatogram (Assay/ RS USP Method)

Standard / System Suitability Chromatogram (Assay/ RS USP Method)

Sample Chromatogram (Assay/ RS USP Method)

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1i14CLEOi)~

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Title

Analytical Method Equivalency and Justification Report for Assay of

T elmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDPI Al2011100S/OO

Page 5 of25

MATERIALS, CHEMICALS AND REAGENTS, INSTRUMENTS I EQUIPMENTS

AND COLUMN USED FOR METHOD EQUIVALENCY
M a t ena
. Is reqUIre
. d
Sr.
WS/RS
Potency I
Material Name
Lot No. I Batch No.
Manufactured by
No.
Purity
No.
Telmisartan working
JWSl111
Macleods
1.
E/9967110005
99.5 %
standard
01500
Pharmaceuticals LTD
Impurity A
(Telmisartan Related
PRL/II9967/RM/561 IS-TELMacleods
2.
99.78 %
compound A USP)
0724
Pharmaceuticals LTD
08
standard
Telmisartan Impurity
IS-TELMacleods
3.
ARD/PREPI111164
92.25 %
B
0768
Pharmaceuticals LTD
PRLlII9967/IMPI11
IS-TELMacleods
4.
Telmisartan Impurity E
98.31 %
7110
0725
Pharmaceuticals LTD
Macleods
PRL/II9967IIMP/07 IS-TEL5.
Telmisartan Impurity F
99.03 %
2/08
0726
Pharmaceuticals LTD
PRLI11996711/127II IS-TELMacleods
6.
Methyl ester Impurity
99.66 %
0728
Pharmaceuticals LTD
0
Telmisartan tablets
Macleods
7.
BTH002B
--80mg
Pharmaceuticals LTD
3.

Placebo for
Telmisartan tablets

8.

--

SSA(856)121A,B,C

Macleods
Pharmaceuticals LTD

--

Chemicals and Reagents used:

Sr. No.

Chemical/Reagent

Lot No.1 Batch No.

Manufactur
ed by

Grade

1.

Water

NA

-----

Milli-Q

2.

Methanol

SKISF11285

Merck

HPLC

3.

Di-basic sodium phosphate

Sodium Hydroxide

Rankem
Thomas
Baker

AR

4.

J059FI0
PH11112032/034911112/01

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mACLEOD~

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Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDP1Al20111008/00

Page 6 of25

5.

Tetrahydrofuran

R158MlO

Rankem

HPLC

6.

Orthophosphoric acid
Ammonium dihydrogen phosphate

Rankem
Thomas
Baker

HPLC

7.

R130Fll
PHl1012535/85910111101

AR

Filter used:
Sr. No.

Name
0.45 ~m Nylon
1.
(membrane disc filter) type HNN
Instruments 1 Equipments used:

Dimension

Make
Advanced Micro devices Pvt Ltd
(Mdi)

25mm

Sr. No.

Instrument 1 Equipment

Make

l.

HPLC

Shimadzu

Instrument 1
Equipment ID
1-155

2.

HPLC

Shimadzu

1-152

YES

3 ..

Analytical Balance

Sartorius

1-92

YES

4.

Analytical Balance

Sartorius

1-93

YES

5.

pH meter

Lab India

1-148

YES

Calibrated
YES

Column used: (for In house method)

Sr. No.
1.

Column
Inertsil ODS-3, (150 mm X 4.6 mm),

5~m

Column Serial
No.
7KI85231

Column ID No.
LC-116108

Column used: (for USP method)

Sr. No.

Column

l.

Kromasil100 -5 C18 (60 mm x 4.0 mm), 5 ~m

Column Serial
No.
E54637

Column ID No.
02COXH002649

Note book used:

Sr. No.

Note book

Reference No.

1.

Analytical Method Validation Note book

LlMEJ/DP/2011l006

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3.2.P.5.3

Page 345

m4CLEOi)~

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Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDP/Al2011100S/00

4.

Page 7 of25

ANALYTICAL METHODOLOGY

ASSAY METHOD (IN HOUSE)

Preparation of buffer pH 3.2:
Dissolve about 3.57 g of dibasic sodium phosphate in 2000 mL water, mix. Adjust the pH of
the solution to 3.2 0.05 with orthophosphoric acid, mix. Filter the solution through
0.45 !lm nylon filter.
For mobile phase, prepare a mixture of buffer pH 3.2, methanol and tetrahydrofuran
(20: 80: 05 v/v/v), degas

4.1 Chromatography condition

i. Chromatographic Mode : Isocratic
ii. Column
: Inertsil ODS-3, (150 mm X 4.6 mm), 5/-lm
iii. Wavelength
: 271 nm
iv. Flow rate
: 1.0 mL / min.
v. Injection volume
: 10 /-lL
vi. Column oven temperature: 50C
vii. Sample temperature
: 1DoC
vii. Run Time
: 6 min

Diluent
Prepare a mixture of methanol and water (50: 50 v/v), degas.

4.2 Procedure
IN sodium hydroxide solution:
Dissolve about 4 g of sodium hydroxide in 100 mL of water, mix.
Blank solution
Use diluent as blank.
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Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDPIAl2011100S/OO

Page S of25

Standard preparation:
Weigh accurately and transfer about 80 mg of Telmisartan reference I working standard to a
100 mL volumetric flask. Add 0.4 mL of IN sodium hydroxide solution and about 75 mL of
methanol and sonicate to dissolve. Allow to equilibrate to room temperature and dilute to
volume with methanol, mix. Dilute 5 mL of the solution to 50 mL with diluent, mix.

Note: Standard preparation is stable up to 48 H at room temperature.

Solution A:
Weigh accurately and transfer about 8 mg of Telmisartan methyl ester impurity standard to a
100 mL volumetric flask. Add about 75 mL of methanol and sonicate to dissolve. Allow to
equilibrate to room temperature and dilute to volume with methanol, mix.
Resolution solution:
Transfer 5 mL each of standard preparation and solution A to a 50 mL volumetric flask and
dilute to volume with diluent, mix.
Sample Preparation:
Weigh 20 tablets and determine the average weight. Crush the tablets to a fine powder.
Weigh accurately and transfer the tablet powder equivalent to about 80 mg of Telmisartan to
a 100 mL volumetric flask. Add 0.4 mL of 1 N sodium hydroxide solution and about 75 mL
of methanol and sonicate for 20 minutes. Allow to equilibrate to room temperature and
dilute to volume with methanol, mix. Filter the solution through 0.45~m nylon (25 mm)
filter; discarding first 3 mL of the filtrate. Dilute 5 mL of the filtrate to 50 mL with diluent,
mIX.

Note: Sample preparation is stable up to 48 H at room temperature.

Placebo Preparation
Weigh the placebo powder equivalent to about 80 mg of Telmisartan to a 100 mL volumetric
flask. Add 0.4 mL of 1 N sodium hydroxide solution and about 75 mL of methanol and
sonicate for 20 minutes. Allow to equilibrate to room temperature and dilute to volume with
methanol, mix. Filter the solution through 0.45~m nylon (25 mm) filter; discarding first 3
mL of the filtrate. Dilute 5 mL of the filtrate to 50 mL with diluent, mix.

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Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDP/A/2011/00S/OO

Page 9 of25

Chromatography Procedure
Equilibrate the column with mobile phase with the chromatographic conditions for stable
baseline.
Inject blank (diluent), placebo, and resolution solution and record the chromatogram.
Inject standard preparation in five replicates and record the chromatogram.
Retention time of Telmisartan peak is between 3.0 min and 4.8 min.
Relative retention time of Telmisartan methyl ester impurity is ~ 1.44 with respect to
Telmisartan.
System suitability criteria
The resolution between Telmisartan and Telmisartan methyl ester peak should not be less
than 2.0.
The relative standard deviation for area of Telmisartan peak for five replicates should not be
more than 2.0 %.
The tailing factor for Telmisartan peak should not be more than 2.0.
The column efficiency for the Telmisartan peak should not be less than 2000 theoretical
plates.
Inject the sample and calculated the % assay.
% Assay of Telmisartan tablets

==

AT
Ws
5
100
50
Aw
------)( --------){ ---------)( ----------)( -------- )(-------)( J?
As
100
50
WT
5
LC

Where,
AT

= Mean area of the peak due to Telmisartan in the chromatogram of sample

preparation.

As

= Mean area of the peak due to Telmisartan in the chromatogram of standard

preparation.

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mACLEOD~

1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDP/Al2011100S/00

Ws

Page 10 of25

= Weight of Telmisartan working/ reference standard taken for standard preparation,

mmg.

WT

= Weight ofa sample taken for sample preparation, in mg.

Aw

= % Assay of Telmisartan working standard, on as is basis.

LC

Average weight of a tablet, in mg.

Label claim of Telmisartan in a tablet, in mg.

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1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRJDPIAf2011/00S/OO

Page 11 of25

ASSAY METHOD (USP 34 NF 29)

PREPARATION OF MOBILE PHASE:
Preparation of diluent:
Methanolic sodium hydroxide solution:
Dissolve about 0.2 gm of sodium hydroxide in 1000 mL of methanol and mix.

Preparation of buffer pH 3.2:

Dissolve about 2 g of ammonium dihydrogen phosphate in 1000 mL water, mix. Adjust the
pH of the solution to 3.0 0.05 with 1M orthophosphoric acid, mix.

Mobile phase:
Methanol and buffer and degas (70: 30) v/v.

CHROMATOGRAPHY CONDITION
Column
Pump mode

: KromasiliOO -5 CI8 (60 mm x 4.0 mm), 5 !-lm

: Isocratic

Flow rate

: 0.7 mL I min

Injection volume

: 5 ilL

Wavelength

: UV, 298 nm

Column temperature

: 40C

Run time

: 25 min

PREPARATION OF SOLUTIONS:
Blank solution
Use diluent as blank.
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1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDPIA/2011100S/OO

Page 12 of25

Standard stock solution preparation for Telmisartan:

Weigh accurately and transfer about 40 mg of Telmisartan working standard in a 50 mL
volumetric flask. Add about 30 mL diluent and sonicate to dissolve. Allow to equilibrate to
room temperature and make up to volume with the diluent, mix.
Standard stock solution preparation for Telmisartan related compound A:
Weigh accurately and transfer about 5 mg of Telmisartan related compound A in a 50 mL
volumetric flask. Add about 30 mL diluent and sonicate to dissolve. Allow to equilibrate to
room temperature and make up to volume with the diluent, mix.
Standard solution preparation:
Transfer 7 mL of Telmisartan standard stock and 6.5 mL of Telmisartan related compound A
to 50 mL volumetric flask and diluted upto the mark with diluent and mix.
Sample solution for Telmisartan Hel tablets 80 mg
Weigh 20 tablets and determine the average weight of the tablets. Weigh 20 intact tablets and
transfer it into 2000 mL volumetric flask. Add about 1600 mL of diluent and swirl to disperse
and sonicate for about 10 minutes. Allow to equilibrate to room temperature and dilute to
volume with diluent and mix. Filter the solution through 0.45j..lm nylon (25 mm) filter,
discarding first 3 mL of the filtrate. Further dilute 7 mL to 50 mL with diluent and mix.
Sample solution for Telmisartan Hel tablets 40 mg
Weigh 20 tablets and determine the average weight of the tablets. Weigh 20 intact tablets and
transfer it into 1000 mL volumetric flask. Add about 800 mL of diluent and swirl to disperse
and sonicate for about 10 minutes. Allow to equilibrate to room temperature and dilute to
volume with diluent and mix. Filter the solution through 0.45j..lm nylon (25 mm) filter,
discarding first 3 mL of the filtrate. Further dilute 7 mL to 50 mL with diluent and mix.
Sample solution for Telmisartan Hel tablets 20 mg
Weigh 20 tablets and determine the average weight of the tablets. Weigh 20 intact tablets and
transfer it into 500 mL volumetric flask. Add about 400 mL of diluent and swirl to disperse
and sonicate for about 10 minutes. Allow to equilibrate to room temperature and dilute to
volume with diluent and mix. Filter the solution through 0.45j..lm nylon (25 mm) filter,
discarding first 3 mL of the filtrate. Further dilute 7 mL to 50 mL with diluent and mix.

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IiIACLEOi);)
I1111111111I1111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDP/A/2011100S/00

Page 13 of25

Placebo Preparation for 80 mg tablets

Weigh the placebo equivalent to 20 tablets of Telmisartan to a 2000 mL volumetric flask.
Add about 1600 mL of diluent and swirl to disperse and sonicate for about 10 minutes.
Allow to equilibrate to room temperature and dilute to volume with diluent and mix. Filter
the solution through 0.45)lm nylon (25 mm) filter, discarding first 3 mL of the filtrate.
Further dilute 7 mL to 50 mL with diluent and mix.
Placebo Preparation for 40 mg tablets
Weigh the placebo equivalent to 20 tablets of Telmisartan to a 1000 mL volumetric flask.
Add about 800 mL of diluent and swirl to disperse and sonicate for about 10 minutes. Allow
to equilibrate to room temperature and dilute to volume with diluent and mix. Filter the
solution through 0.45)lm nylon (25 mm) filter, discarding first 3 mL of the filtrate. Further
dilute 7 mL to 50 mL with diluent and mix.
Placebo Preparation for 20 mg tablets
Weigh the placebo equivalent to 20 tablets of Telmisartan to a 500 mL volumetric flask. Add
about 400 mL of diluent and swirl to disperse and sonicate for about 10 minutes. Allow to
equilibrate to room temperature and dilute to volume with diluent and mix. Filter the
solution through 0.45)lm nylon (25 mm) filter, discarding first 3 mL of the filtrate. Further
dilute 7 mL to 50 mL with diluent and mix.
Impurity solutions (For specificity study)
Impurity A
Weigh accurately about 1 mg of Impurity A and transfer in to a 100 mL volumetric flask;
add about 70 mL of diluent and sonicate to dissolve. Dilute to volume with diluent and mix.
Dilute further 5 mL of this solution to 50 mL with mobile phase and mix.
Impurity B
Weigh accurately about 1.5 mg of Impurity B and transfer in to a 100 mL volumetric flask;
add about 70 mL of diluent and sonicate to dissolve. Dilute to volume with diluent and mix.
Dilute further 5 mL of this solution to 50 mL with mobile phase and mix.

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mACLEOD:)
1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDPI A12011100S/OO

Page 14 of25

Impurity E
Weigh accurately about 1 mg of Impurity E and transfer in to a 100 mL volumetric flask; add
about 70 mL of diluent and sonicate to dissolve. Dilute to volume with diluent and mix.
Dilute further 5 mL of this solution to 50 mL with mobile phase and mix.
Impurity F
Weigh accurately about 1 mg ofImpurity F and transfer in to a 100 mL volumetric flask; add
about 70 mL of diluent and sonicate to dissolve. Dilute to volume with diluent and mix.
Dilute further 5 mL of this solution to 50 mL with mobile phase and mix.
Impurity Telmisartan methyl ester
Weigh accurately about 1 mg of Telmisartan methyl ester and transfer in to a 100 mL
volumetric flask; add about 70 mL of diluent and sonicate to dissolve. Dilute to volume with
diluent and mix.
Dilute further 5 mL ofthis solution to 50 mL with diluent and mix.

Chromatography Procedure
Equilibrate the column with mobile phase with the chromatographic conditions for stable
baseline.
Inject blank (diluent), placebo and resolution solution and record the chromatogram.
Inject standard preparation in five replicates and record the chromatogram.

Retention time of Telmisartan peak is between 1 minute to 3 minutes

System suitability criteria

Resolution between Telmisartan and Telmisartan related compound A should not be less
than 3.0.
The relative standard deviation of the area due to Telmisartan peaks in five replicate
injections of the standard solution should not be more than 2.0 %.
The tailing factor for Telmisartan peak should not be more than 2.0.
Capacity factor should not be less than 1.5.

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m4CLEOD~

1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDP/A12011100S/00

Page 15 of25

Inject the sample solution and calculate the % assay.

% Assay of Telmisartan tablets 80 mg

Ar
Ws
7
2000
50
Aw
------)( -------J( ---------)(--------J( ----------- J(----------)( }l
As
50
50
Wr
7
LC

==

% Assay of Telmisartan tablets 40 mg

Ar
Ws
7
1000
50
Aw
------J( -------J( ---------J(--------J( ----------- J(---------J( Jl
As
50
50
Wr
7
LC

% Assay of Telmisartan tablets 20 mg

Ar
Ws
7
500
50
Aw
------J( -------J( ---------J(--------J( ----------- J(---------J( Jl
As
50
50
Wr
7
LC

Where,
Ar

Mean area of the peak due to Telmisartan in the Sample preparation

As

Mean area of the peak due to Telmisartan in the Standard preparation

Ws

Weight of Telmisartan reference standard used in standard preparation (mg)

Wr

Weight of sample taken for sample preparation (mg)

Jl

= % Assay of Telmisartan reference standard (As is basis).

Aw

Average weight of a tablet (mg).

LC

Label claim of tablet (mg).

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111111111111 1111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRJDPIAf2011100S/OO

Page 16 of25

RESULTS AND OBSERVATION

5.1 SPECIFICITY (INTERFERENCE STUDY) INHOUSE METHOD
The blank, placebo solution, impurity solutions, standard solution and sample solution were
prepared and injected as described in the methodology. The obtained results are presented in the
result table.
Result table 5.la.l
Name of solution

R.T (Minutes)

Blank

No interference observed

Placebo

No interference observed

Telmisartan Methyl Ester Impurity ID

4.70

Telmisartan related compound A

2.35

Telmisartan Impurity B

3.08

Telmisartan Impurity E

2.63

Telmisartan Impurity F

2.63

Telmisartan in standard

3.35

Telmisartan in sample

3.35

Specificity for inhouse impurities covered under Telmisartan Tablets Assay method validation
(Reference Report No. AVRlDP/201O/HPLCI023/00)
Conclusion
Based on the obtained result it is concluded that there is no interference observed due to blank,
impurities and placebo at the retention time of Telmisartan in standard solution and sample
solution chromatograms as per Inhouse method

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Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRJDP/Al2011100S/00

Page 17 of25

SPECIFICITY (INTERFERENCE STUDy) USP METHOD

The blank, placebo solution, known impurities solutions, standard solution and sample solution
were prepared and injected as described in the methodology. The obtained results are presented
in the result table.
N arne of solution

Retention time (Minutes)

Blank

No interference observed

Placebo

No interference observed

Telmisartan Methyl Ester Impurity ID

2.98

Telmisartan related compound A

0.99

Telmisartan Impurity B

1.64

Telmisartan Impurity E

1.70

Telmisartan Impurity F

1.27

Telmisartan in standard

2.05

Telmisartan in sample

2.05

Conclusion
Based on the obtained result it is concluded that there is no interference observed due to blank,
and placebo at the retention time of Telmisartan in standard solution and sample solution
chromatograms as per USP method.

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1i14CLEOD~

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Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDP/A/20111008/00

Page 18 of25

5.2 PRECISION STUDY (In house method)

System precision
To check system precision, standard solution was prepared as per methodology and peak
responses were measured in five replicates. The mean and relative standard deviation was
calculated. The results are presented in the following result tables.

R esult t abi e or TeImlsa

. rt an Tabi et s 80 mg
Injection No.

Peak Area

1719939

1723529

1722861

1722208

1718993

Mean

1721506

%RSD

0.11

Conclusion

The relative standard deviation for areas of peak due to Telmisartan for five replicate
injections of the standard solution is 0.11 %, which is well within the acceptance criteria of
not more than 2.0 %.

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1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

T elmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDPI AJ2011100S/00

Page 19 of25

REPEEAT ABILITY
The assay was carried out as described in the methodology on six samples prepared from crushed
tablet powder of Telmisartan Tablets 80 mg, and the % assay of Telmisartan was calculated. The
mean and relative standard deviations of the results were calculated. The results' obtained for are
presented in the following result table.
% Assay

Sample preparation no.

Telmisartan Tablets SO mg
1

98.1

97.6

98.1

98.2

97.9

98.3

Mean

9S.0

%RSD

0.26

Conclusion
The relative standard deviation of the assay results for six individual sample preparations in
the repeatability study are 0.26 % Telmisartan tablets 80 mg which is well within the
acceptance criteria of not more than 2.0 % and also not less than 90.0 % and not more than
110.0 %.

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m4CLEOD~

1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDPI Al20111008/00

Page 20 of25

PRECISION STUDY (USP method)

System precision
To check system precision, standard solution was prepared as per methodology and peak
responses were measured in five replicates. The mean and relative standard deviation was
calculated. The results are presented in the following result table.
Result table for Telmisartan Tablets 80 mg
Injection No.

Peak Area

2586280

2586891

2585946

2587122

2586119

Mean

2586472

%RSD

0.02

Conclusion
The relative standard deviation for areas of peak due to Telmisartan for five replicate
injections of the standard solution is 0.02 %, which is well within the acceptance criteria of
not more than 2.0 %.
,
i

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1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRfD PIAl2011100S/00

Page 21 of25

REPEEAT ABILITY

The assay was carried out as described in the methodology on six samples prepared from intact
tablet of Telmisartan Tablets 80 mg, and the % assay of Telmisartan was calculated. The mean
and relative standard deviations of the results were calculated. The results obtained for assay are
presented in the following result table.
% Assay

Sample Preparation no.

Telmisartan Tablets SO mg

99.9

99.4

98.9

98.9

98.8

99.2

Mean

99.2

%RSD

0.42

Comparative Results

F or T eImlsa
. rtan tablets SO mg
% Assay of Telmisartan HCI

Mean of Repeatability (In house method)

98.0

Mean of Repeatability (USP method)

99.2

Absolute difference

1.2

I
i

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O~\'c.\'\

1i14CLEOi)~

1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

T elmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDPI AJ2011100S/OO

Page 22 of25

Conclusion
The relative standard deviation of the assay results for six individual sample preparations in the
repeatability study are 0.42 % for Telmisartan tablets 80 mg, which is well within the
acceptance criteria of not more than 2.0 % and also not less than 90.0 % and not more than
110.0 %.
The absolute difference between the mean assay results obtained by In House method and by
USP method is 1.2 for Telmisartan 80 mg tablets which is well within the acceptance criteria
of not more than 2.0.

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Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDP1Al20111008/00

5.3

Page 23 of25

System suitability (In house method)

To check system suitability, Telmisartan standard solution was prepared as described in the
methodology. The standard solution was injected in five replicates before starting each
method equivalency p'arameter and peak responses were measured. The system suitability
parameters of relative standard deviation, tailing factor and theoretical plates for the peak
due to Telmisartan along with resolution between Telmisartan & Telmisartan methyl ester
was also calculated. The comparative results are presented in the following result table
(Comparative data of system suitability)
Resolution
%RSD
between
Theoretical Telmisartan
(five
Mean Area
&
plates
replicate
Telmisartan
injections)
methyl ester

Sr.
No.

Validation
parameters

Retention
time
(Minutes)

Tailing
Factor

Specificity

3.4

1.3

2782

4.1

1721506

0.11

Repeatability

3.4

1.3

2782

4.1

1721506

0.11

System suitability (USP method)

To check system suitability, Telmisartan standard solution was prepared as described in the
methodology. The standard solution was injected in five replicates before starting each
method equivalency parameter and peak responses were measured. The system suitability
parameters of relative standard deviation, tailing factor, capacity factor and resolution
between Telmisartan and Telmisartan related compound A was calculated. The comparative
results are presented in the following result table

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Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDPI Al2011100S/OO

Page 24 of25

(Comparative data of system suitability)

Sr.
No.

1
2

%RSD
(five
Mean Area
&
replicate
Telmisartan
injections)
RCA

Validation
parameters

Retention
time
(Minutes)

Tailing
Factor

Capacity
factor

Specificity (1)

2.1

1.3

1.6

5.0

2586472

0.02

Specificity (2)

2.0

1.2

1.5

4.9

2575528

0.07

Repeatability

2.1

1.3

1.6

5.0

2586472

0.02

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Resolution
between
Telmisartan

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(Y&'\2-\')

mACLEOiD~

1111111111111111111111111111

Title

Analytical Method Equivalency and Justification Report for Assay of

Telmisartan

Product Name

Telmisartan Tablets

Report No.

MEJRlDP IA/20111008/00

Page 25 of25

I
I

JUSTIFICATIONI SUMMARY OF THE REPORT

Assay method
Specification comparison
Acceptance criteria
As per Inhouse

Telmisartan He}
% Assay

Not less than 90.0% and not

more than 110.0%

Acceptance criteria
As per USP
Not less than 90.0% and not
more than 110.0%

Specificity:
Based on the specificity study in both the methods (Inhouse validated method and USP
method) it is concluded that there is no interference observed due to blank and placebo
and impurities at the same retention time as that of Telmisartan peak.
However the assay results for Telmisartan tablets 80 mg by both the methods i.e. In
house method and USP method are equivalent.
Based on the above observation, it was decided to continue using in house validated
assay method for all the strengths of Telmisartan tablets 20 mg, 40 mg and 80 mg.

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