VERITAS PHARMACEUTICALS LIMITED,

Muradpur, Vannara, Mouchak, Gazipur, Bangladesh

7/ffi-rltms

STANDARD TEST PROCEDURE

Name of Material: Montelukast Sodium INN

Document No.: TP/1 1 13010/0'l lssue Date : 2}lllar 2014

Version No.: 01 Superseded doc. No,: VRMA/M/O1 121007 Review Date : 19 I'Aar 2017

Approval of Current Version of the Document

Name Job Title Signature & Date

Prepared by Md. Monjur Rahman Executive, Quality Control NU^^-\tv

\t/dg /t4
Checked by Md, Rajibul Al Azad Sr. Executive, Quality Control
@r*tralry
Agreed by Md. Tarikul lslam Bossunia Asst. Manager Quality Conkol
Gffirrr
Approved by Md. Moniruzzaman Quality Assurance Manager
b"o- wf\gll\
Ref. Method: INN Storage Condition: Preserve in air tight containers.

Retest Validity: 24 months Action & Use: Anti-Asthmatic

CONTENT

1. Appearance
2. Solubility
3. ldentification
4. Water by Karl fisher
5. Heavy metals
6. Specific optical Rotation
7. Related substances
B. Assay
9. Revision History

DISTRIBUTION LIST

QC Laboratory 01

This document is Effective from the Date of the Approval.

WITHOUT PERMISSION FROM HEAD OF QUALITY ASSURANCE OR HIS/HER DELEGATE, COPY OF THIS DOCUMENT IS

STRICTLY PROHIBITED

Page 1 of 5
 VERITAS PHARMAGEUTICALS LIMITED,

ffiritas Muradpur, Vannara, Mouchak, Gazipur, Bangladesh

STANDARD TEST PROCEDURE

Material Name: Montelukast Sodium INN

Doc. No.: TP/1 1 13010/01 Version:01 Prepared rr IH,*I* Approved

1. Appearance

Procedure:
Take about 1 gm of sample in a watch glass and observe for its physical appearance, color, etc. using a white background.

Acceptance criteria: White to pale yellow hygroscopic powder.

2. Solubility

Procedure: Take sample in test tube, add sufficient measured amount of solvent to dissolved the material then depend the
solubility from table below:

able-1:
Descriptive term Approximate volume of Solvent in milliliters per gram of solute
Very soluble Less than 1

Freely soluble From 1 to 10

Soluble From 10 to 30

Sparingly soluble From 30 to 100

Slightly soluble From 100 to 1 000

Very slightly soluble From 1 000 to 10 000

Practically insoluble More than 10 000

able-2: Solubility Test

Specification Solvent Sample to be Solvent to add Result Remarks

taken about

Freely soluble Ethanol (96%), 1g 10 ml A clear solution Meets

water

methanol

Practically Acetronitrile 10 mg More than 100 ml Does not dissolve Meets

insoluble

Acceptance criteria: Freely soluble in ethanol (96%), in water and in methanol, and practically insoluble in acetonikile.

3. ldentification

A. lnfrared absorption spectrum

Procedure:
Sample preparation: Weigh 1 to 2 mg of the sample and weigh 300 to 400 mg of fine dry powder of potassium bromide.
Carefully grind the mixture, spread it uniformly in a suitable die, and submit it to a pressure of about 80 KN. Transfer the
disc into the sample holder cup and record the lR spectrum.

Standard preparation: Weigh 1 to 2 mg of the Montelukast sodium WS and weigh 300 to 400 mg of potassium bromide.
Carefully grind the mixture, spread it uniformly in a suitable die, and submit it to a pressure of about B0 KN. Transfer the
disc into the sample holder cup and record the lR spectrum.

Page 2 of 6
 VERITAS PHARMACEUTICALS LIMITED,
Muradpur, Vannara, Mouchak, Gazipur, Bangladesh
#eritms
STANDARD TEST PROCEDURE

MaterialName: Montelukast Sodium INN

By:
Doc. No.: TP/1 1'l 3010/01 Version:01 Prepared
ffi,i Approved ey :
;p*$*nr,1'1
Acceptance criteria: The infrared absorption spectrum of sample is concordant with the reference spectrum or the
spectrum obtained from Montelukast sodium WS.

B. Sodium test

Dissolve 0.1 g of the substance to be examined in 2 mL of water or use 2 mL of the prescribed solution. Add 2 mL of a 1 50
g/L solution of potassium carbonate and heat to boiling. No precipitate is formed. Add 4 mL of potassium pyroantimonate
iolutionandheattoboiling.Allowtocoolinicedwaterandif necessaryrubtheinsideofthetesltubewithaglassrod.

g potassium antimonate(V)
[Potassium Antimonate(V) Solution/ Potassium pyroantimonate solution: Dissolve 2 of
in

95 mL of hot water, cool rapidly and add a solution containing 2.5 g ol potassium hydroxide in 50 mL of water and 1 mL of
2M sodium hydroxide. Allow to stand for 24 hours, filter and dilute to 150 mL with water.l

Acceptance criteria: A dense white precipitate is formed.

4. Water

Take approximately 0.1 00 mg of sample and determine the water content using Karl Fisher apparatus.

Acceptance criteria: Not more than 4.0%

5. Heavy Metals:

Lead Nitrate Stock Solution

Dissolve 159,8 mg of lead nitrate in 100 ml of water to which has been added 1 ml of nitric acid, then dilute with water tc 1000
ml. Prepare and store this solution in glass containers free from soluble leadsalts. \

Standard Lead Solution

On the day of use, dilute 10.0 ml of Lead Nitrate Stock Solution with water to 100.0 ml. Each ml of Standard Lead Solution
contains the equivalent of 10 pg of lead. A comparison solution prepared on the basis of 100 pl of Standard Lead Solution per
g of substance being tested contains the equivalent of 1 part of lead per million paris of substance being tested.

Thioacetamide reagent R
To 0.2 ml of thioacetamide solution (40g/l in water) add 1 ml of a mixture of 5 ml of water, 15 ml of '1 M sodium hydro'xide and
20 ml of glycerol(857.), heat in a water bath for 20s. Prepare immediately before use.

pH 3.5 Acetate Buffer

Dissolve 25 g of ammonium acetate in 25 ml of water, and add 38,0 ml of 6 N hydrochloric acid. Adjust, if necessary, with 6 N
ammonium hydroxide or 6 N hydrochloric acid to a pH of 3.5, dilute with water to 100 ml, and mix.

Test Preparation
Dissolve 1.0 g in 1.2 ml of acetone R and dilute to 20 ml with water.

Standard Preparation
Prepare a mixture of 10 ml of lead standard solution and 2 ml of the test solution in acetone.

Blank solution
Prepare a mixture of 1 0 ml acetone and 2 ml of test solution.

Procedure

Page 3 of 5
 VERITAS PHARMACEUTICALS LIMITED,
ffieritas Muradpur, Vannara, Mouchak, Gazipur, Bangladesh

STANDARD TEST PROCEDURE

Material Name: Montelukast Sodium INN

Doc. No.: TP/1 1 13010/01 Version: 01 Prepared By: tr74v.\ J Approved By:
\*/r;gi t,

To each of the solution add 2 ml of buffer solution pH 3.5. Mix and add to 1.2 ml of thioacetamide reagent. Mix immediately.
Examine the solution after two minutes. Any brown color in the test solution is not more intense than that in
the referenie
solution.

Acceptance criteria: Maximum 20 ppm.

6. Specific optical rotation

Prepare a solution by dissolving 1.0 g of the sample in 100m1 of Methanol and mix well. Determine the
specific optical rotation
within 15 minutes.

Calculation:
Angle of rotation X 100 X 1 00
Specific optical rotation =
2 X Sample weight X (100 - % of water)

Acceptance criteria: +95.00 to +106.00 on Anhydrous Basis

7. Related substances ( by HPLC)

Mobile phase and chromatographic system- prepare as directed in the Assay.

Test solution preparation:

Weigh and transfer accurately about 50.0 mg of Montelukast Sodium sample into a clean Ory lbOml standard volumetric
flask.
Add about 60ml diluting solution. Shake well and Sonicate for 5 minutes. Make volume wlth same diluting
solution and mix
well. Filter it through 0.45 micron PTFE- membrane disk filter.

Single maximum impurity peak =

Jhe Area of the individual impurity peak in the test solution x 1.0

Acceptance criteriat Not more than 1.0%

Total impurities =
The Area of the total impurity peaks in the test solution x 2.0

Acceptance criteria: Not more than 2.0%

8. Assay

Chromatographic Svstem:
Apparatus : perkin Ermer Frexure HpLC
with pDA Detector
Column : Cts, 150mmx4.6mm, 5p or equivalent

Mobile Phase : Weigh-accurately 1.9g of ammonium acetate, transfer into 500m1 of beaker,
add s00mt of water and dissotve proierty. Adjust the pH 3.st0.05 with
Gtacial Acetic acid : Methanot(15:85)

Page 4 of 6
 VERITAS PHARMACEUTICALS LIMITED,
#britas Muradpur, Vannara, Mouchak, Gazipur, Bangladesh

STANDARD TEST PROCEDURE

Material Name: Montelukast Sodium INN

Doc. No.: Version: Prepared By: Approved aV'5y45, o9' \Y

TP/1 1 13010/01 01
rcH,I,
Diluting solution : Water: Methanol ( 30 : 70 )

Temperature : Ambient (30'C)

FIow rate : 2.0 ml/min

Monitoring wavelength : 254nm

Load : 10 pl

Retention Time : 4-6

Standard preparation:

Weigh and transfer accurately about'10,0 mg of working standard of Montelukast Sodium into a clean dry 100m1 standard
volumetric flask. Add about 60ml diluting solution. Shake well and Sonicate for 5 minutes. Make volume with same diluting
solution and mix well. Filter it through 0 20 micron PTFE- membrane disk filter.

Sample preparation:

Weigh and transfer accurately about 10.0 mg of Montelukast Sodium sample into a clean dry 100m1 standard volumetric flask.
Add about 60ml diluting solution. Shake well and Sonicate for 5 minutes. Make volume with same diluting solution and mix
well. Filter it through 0.20 micron PTFE- membrane disk filter

Svstem suitabilitv test:

Parameter : Acceptance criteria !

lnjection six replicate of standard solution : RSD Not more than 2.0%

Place vials containing diluting solution as blank, standard preparation A and sample preparation B into the tray of the auto
sampler of Perkin Elmer Flexure HPLC. Run the instrument and record the chromatogram. Calculate the quantity of
Montelukast Sodium in sample using the following equation:

Calculation:

Content of Montelukast Sodium

Au Ws Potency of std.
= ----- x ---x -------------- x 100
As Wu 100

Where,
As = Peak area of the standard preparation
Au = Peak area of the sample preparation
Ws = weight of the standard taken
Wu = weight of the sample taken

Acceptance criteria: 98.0% to 102.0% on anhydrous basis.

Page 5 of 6
 VERITAS PHARMACEUTICALS LIMITED,
ffieritas Muradpur, Vannara, Mouchak, Gazipur, Bangladesh

STANDARD TEST PROCEDURE

MaterialName: Montelukast Sodium INN

By:
Doc, No.: TP/1 1 13010/01 Version:01 Prepared
ffii,o Approved aV,
,p@,rv't-
Revision History

Document No. Version,No Date Reason

vRMtuM/o112t007 00 Aug2012 lnitial test procedure of Montelukast Sodium INN

TP/1 1 13010/01 01 l,lar-2014 To detail the procedure for analysis of Montelukast Sodium INN

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