ETHICAL DRUGS LTD.

SIDDHIRGANJ, NARAYANGANJ.
IN-HOUSE SPECIFICATIONS OF RAW MATERIALS

Dept. Document No. Material ID Code Version No. Effective Date Page
Quality Control QC/SPE/A A 00 01.04.13 1 of 1

Title : TEST PROCEDURE OF MONTELUKAST SODIUM

Mol. Wt. : 608.18 Mol. Formula: C35H35 ClNNaO3S

TESTS : SPECIFICATIONS

01. DESCRIPTION : White to yellow hygroscopic powder.

02. SOLUBILITY : Freely soluble in methanol.

03. IDENTIFICATION : IR absorption spectrum should be identical to that of Working

Standard.
04. WATER (By KF) : NMT 2.0%
05. HEAVY METALS : NMT 20ppm

6. RELATED SUBSTANCES
(HPLC)

a) SINGLE HIGHEST IMPURITY : NMT 0.75%

b) TOTAL IMPURITIES : NMT1.5%
07. ASSAY (HPLC, OAB) : 98.0% to 102.0%

08. PACKAGING INFORMATION :

Container : Fiber board drum/equivalent
Pack size : 25.0 Kg/ suitable quantity
Label : Manufacturer /Origin
Gross Weight :
Tare Weight :
Net Weight :
Batch No./ lot No. :
Manufacturing Date :
Expiry Date :
Storage condition : Store in an airtight container under nitrogen
pressure, protected from light and moisture.

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Date : Date : Date :
 ETHICAL DRUGS LTD.
SIDDHIRGANJ, NARAYANGANJ.
TEST PRCOCEDURE OF RAW MATERIALS

Dept. Document No. Material ID Code Version No. Effective Date Page
Quality Control QC/STP/A A 00 01.04.13 1 of 8

Title : TEST PROCEDURE OF MONTELUKAST SODIUM

Mol. Wt. : 608.18 Mol. Formula: C35H35 ClNNaO3S

01. DESCRIPTION : Place 1-2 g sample in a petridish and observe visually for its
color.
02. SOLUBILITY : Dissolve 1.0 gm of sample in 10 ml of methanol and it should be
completely dissolved.
03. IDENTIFICATION : a) By IR
Take about 4mg of sample and about 300mg of dried KBr, mix
thoroughly and prepare a pellet. Run the instrument using
standard operating procedure. Take the spectrum and
compare it with spectrum of reference/ working standard
of Montelukast Sodium. Both the spectra should match
in principal.

b) By Test for Sodium

Dissolve 0.1gm of the sodium compound in 2ml of water.
Add 2ml of 15% w/v solution of potassium carbonate and
heat to boiling. No precipitate is formed. Add 4ml of
potassium pyroantimonate TS, and heat to boiling. Allow
to cool in ice water and if necessary, rub the inside of
the test tube with a glass rod. A dense precipitate is formed.
04. WATER (by KF in methanol) : Determine the water content of the material by using Digital
Karl Fischer Titrator (VEEGO VEGONMATIC-MD, India)
or equivalent.

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Designation : QC Officer Designation : Sr. QC Officer Designation : QC Manager

Date : Date : Date :
 ETHICAL DRUGS LTD.
SIDDHIRGANJ, NARAYANGANJ.
TEST PRCOCEDURE OF RAW MATERIALS

Dept. Document No. Material ID Code Version No. Effective Date Page
Quality Control QC/TEST/A009 A009 00 01.04.13 2 of 8

Title : TEST PROCEDURE OF MONTELUKAST SODIUM

Mol. Wt. : 608.18 Mol. Formula: C35H35 ClNNaO3S

05. HEAVY METALS :

Reagents: (i) Thioacetamide glycerin base TS: Mix 2 ml of thioacetamide TS

in 10 ml of glycerin base TS, heat in a boiling water bath for 20 seconds.
Use the mixture immediately.

(ii) Thioacetamide TS: Dissolve 4g thioacetamide in 100 ml of water

(iii) Glycerin Base TS: to 200g of glycerin add water to bring total weight to 235 g.
Then add 142.5 ml of IN sodium hydroxide and 47.5 ml water.

(iv) pH 3.5 Acetate Buffer: Dissolve 25.0g of ammonium acetate in 25ml water and
38.0 ml of 10N HCl. Adjust, if necessary, with 6N ammonium hydroxide or 6N
HCl to a pH of 3.5, dilute with water to 100 ml and mix.

Lead nitrate stock solution : Dissolve 159.8 mg of lead nitrate in 100 ml of water and add 1 ml of concentrated
nitrate acid. Dilute to 1000ml with water.

Standard lead solution : Dilute 10 ml of lead nitrate stock solution to 100 ml with water. ( 10 mcg/ml ) :

Standard preparation: Take 2 ml of standard lead solution in 50 ml Nessler cylinder, add 25 ml of water
and mix. Adjust pH of the solutions between 3-4 with dilute acetic acid or 6N
ammonia. Make upto to 40 ml with water.

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Designation : QC Officer Designation : Sr. QC Officer Designation : QC Manager

Date : Date : Date :

ETHICAL DRUGS LTD.

SIDDHIRGANJ, NARAYANGANJ.
 TEST PRCOCEDURE OF RAW MATERIALS

Dept. Document No. Material ID Code Version No. Effective Date Page
Quality Control QC/TEST/A009 A009 00 01.04.13 3 of 8

Title : TEST PROCEDURE OF MONTELUKAST SODIUM

Mol. Wt. : 608.18 Mol. Formula: C35H35 ClNNaO3S

Test Preparation: Weight 1.0 g of sample in a silica crucible and add enough concentrated
sulphuric acid in order to humidify the powder. Heat slowly until complete
ignition. Add to the carbonized mass, 2 ml concentrated nitric acid and
5 drops of concentrated sulphuric acid. Heat until total disappearance of
white fumes at 500-600º C until compete ignition, cool, add 4 ml
of 6N HCl, cover and digest on a steam bath for 15 minutes.
Uncover and slowly evaporate on steam bath to dryness. Humidify
the residue with one drop of concentrated HCl, add 10 ml of hot water and
digest for 2 minutes.

Add solution till the drop by drop 6N ammonia solution becomes

slightly alkaline to litmus paper, dilute it in 25 ml of water and
readjust pH to 3-4 with 1N acetic acid . Filter if necessary. Transfer
the solution in a 50 ml Nessler cylinder. Wash the crucible with water
and transfer the solution in the cylinder containing the sample
Dilute upto 35 ml with water.

Procedure : To each of the tubes containing the standard preparation and the test
preparation, dd 2 ml of pH 3.5 acetate buffer, then add 1,2 ml of
thioacetamide glycerin base TS, dilute with water to 50 ml, mix and allow
to stand for 2 minutes and view downwards over a white surface
The color of solution from the test preparation is not darker than that of the
solution from standard preparation. downwards cover a white surface.

06. RELATED SUBSTANCES:

(by HPLC)
Reagents: Acetic acid ( AR Grade )
Methanol ( HPLC Grade)
Triethylamine ( HPLC Grade)
Water ( HPLC Grade )
Ammonium acetate ( HPLC Grade )

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Designation : QC Officer Designation : Sr. QC Officer Designation : QC Manager

Date : Date : Date :
 ETHICAL DRUGS LTD.
SIDDHIRGANJ, NARAYANGANJ.
TEST PRCOCEDURE OF RAW MATERIALS

Dept. Document No. Material ID Code Version No. Effective Date Page
Quality Control QC/TEST/A009 A009 00 01.04.13 4 of 8

Title : TEST PROCEDURE OF MONTELUKAST SODIUM

Mol. Wt. : 608.18 Mol. Formula: C35H35 ClNNaO3S

Mobile phase (A) : Dissolve about 3.85 gm of ammonium acetate in 1000 ml of water and add 1ml of
trimethylamine, adjusted pH 5.5 with glacial acetic acid.

Mobile phase (B) : Methanol

Preparation of Diluent : Water : Methanol

20 : 80

Chromatographic
Conditions

Column : Hypersil C-18 (150 mm 4.6 mm)

Flow rate : 1.0 ml /min
Detector : UV at 240 nm
Injection volume : 20 µl
Run Time : 70.0 min

Gradient profile MP(A) MP(B)

Time (min) ( %) ( %)

00 40 60
20 30 70
45 20 80
55 15 85
60 15 85
65 40 60
70 40 60

Retention time of
Montelukast Sodium 37 min (approx.)

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Designation : QC Officer Designation : Sr. QC Officer Designation : QC Manager
Date : Date : Date :

ETHICAL DRUGS LTD.

SIDDHIRGANJ, NARAYANGANJ.
TEST PRCOCEDURE OF RAW MATERIALS

Dept. Document No. Material ID Code Version No. Effective Date Page
Quality Control QC/TEST/A009 A009 00 01.04.13 5 of 8

Title : TEST PROCEDURE OF MONTELUKAST SODIUM

Mol. Wt. : 608.18 Mol. Formula: C35H35 ClNNaO3S

Preparation of Blank : Use diluent as blank.

Reference Solution (a) : Weigh accurately about 100mg of Montelukast Sodium standard in 100ml
volumetric flask. Dilute with diluent.

Reference Solution (b) : Dilute 10ml of reference solution(a) to 100ml with mobile phase Dilute 3.0 ml of
this solution 100ml with mobile phase.

Preparation of Sample
Solution : Accurately weigh and transfer about 100 mg of sample to 100ml of volumetric
flask. Dissolve in diluent by sonication if necessary and dilute to volume with
diluent.

Procedure : Inject 20 µl each of Blank ( diluents ) and reference solution (b) in duplicate. The
system in suitable if the RSD between two injectable is NMT 10%. Inject 20 µl of
sample solution. The relative retention time with reference to Montelukast for
Montelukast sulphoxide isomers about 0.66 and 0.69 and for Montelukast styrene
is about 1.38. Examine the blank run chromatogram for any extraneous peaks and
disregard peaks due to blank.
Calculation : AT x wt std x 10 x 3 x 100 x potency of std
Any (%) impurity = ------------------------------------------------------
AS x 100 x 100 x 100 x wt. of sample

ATT x wt of std. x 10 x 3 x 100 x potency of std

Total impurities = ----------------------------------------------------------------
AS x 100 x 100 x 100 x wt. of sample

Where,
AT = Areas of individual impurity in test
ATT = Sum of all impurities in test
AS = Average area of reference solution (b)

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Designation : QC Officer Designation : Sr. QC Officer Designation : QC Manager
Date : Date : Date :

ETHICAL DRUGS LTD.

SIDDHIRGANJ, NARAYANGANJ.
TEST PRCOCEDURE OF RAW MATERIALS

Dept. Document No. Material ID Code Version No. Effective Date Page
Quality Control QC/TEST/A009 A009 00 01.04.13 6 of 8

Title : TEST PROCEDURE OF MONTELUKAST SODIUM

Mol. Wt. : 608.18 Mol. Formula: C35H35 ClNNaO3S

07. ASSAY (HPLC, OAB) :
Chromatographic conditions :
Column Hypersil ODS, 150 x 4.6 mm. ID 5µ particle size or equivalent.
Flow Rate 1.5 ml/min
Injection Volume 20 µ l
Wavelength 240 nm
Run Time 25 min
Retention Time 7 min aprox.
Buffer preparation Dissolve about 3.85 gm of ammonium acetate in 1000 ml of water and
add 1 ml of trimethylamine, adjusted pH 5.5 with glacial acetic acid.

Mobile phase Methanol : Buffer

780 : 220

Diluent Methanol : Water

80 20

Standard Preparation Weigh accurately about 50 mg of Montelukast SodiumWorking Standard in

(A & B) 100 ml volumetric flask. Dissolve it in diluent and make volume up to the
mark with diluent (ref. soln. A)

Further, take 5 ml of this solution in 50 ml volumetric flask and make volume

upto mark with diluent (ref. soln. B)

Sample Preparation Weigh accurately about 50 mg of Montelukast Sodium in 100 ml

(i & ii) volumetric flask. Dissolve it in diluent and make volume up to the mark
with diluent ( soln. i)

Further, take 5 ml of this solution in 50 ml volumetric flask and make volume

upto mark with diluent (soln. ii).

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Designation : QC Officer Designation : Sr. QC Officer Designation : QC Manager
Date : Date : Date :

ETHICAL DRUGS LTD.

SIDDHIRGANJ, NARAYANGANJ.
TEST PRCOCEDURE OF RAW MATERIALS

Dept. Document No. Material ID Code Version No. Effective Date Page
Quality Control QC/TEST/A009 A009 00 01.04.13 7 of 8

Title : TEST PROCEDURE OF MONTELUKAST SODIUM

Mol. Wt. : 608.18 Mol. Formula: C35H35 ClNNaO3S

Procedure & System The following system suitability criteria should be met prior on injection
Suitability of the sample preparation.

i) Perform one injection of blank.

ii) Inject one injection of standard preparation (A).
iii) Inject five repeat injections of standard preparation (B) & calculate
the similarity factor between standard preparation (A) & 1st
injection of standard preparation (B) by the following formula.

Similarity Factor =

Area of std. preparation (1) Wt. of std. preparation (2)

------------------------------------------------------ × ---------------------------------------
Area of 1st injection of std. preparation (2) Wt. of Std. p[reparation (1)

The similarity factor should be between 0.98 to 1.02. The % RSD of

5 injections of standard preparation (B) should not be more than 1%.

iv) Tailing factor of standard preparation A should be more than 2.0.

v) Theoretical plates of standard preparation A should not be

less than 2000.

vi) Inject one injection each of two individual test preparation.

For better clarity the above inje4ction sequence is summarized

as below:

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Designation : QC Officer Designation : Sr. QC Officer Designation : QC Manager

Date : Date : Date :

ETHICAL DRUGS LTD.

SIDDHIRGANJ, NARAYANGANJ.
TEST PRCOCEDURE OF RAW MATERIALS

Dept. Document No. Material ID Code Version No. Effective Date Page
Quality Control QC/TEST/A009 A009 00 01.04.13 8 of 8

Title : TEST PROCEDURE OF MONTELUKAST SODIUM

Mol. Wt. : 608.18 Mol. Formula: C35H35 ClNNaO3S

Sl. No. Test No. of Injections

i Blank 1
ii STD. A 1
iii STD. B 5
iv Test i 1
v Test ii 1

Calculate the assay of both sample preparation separately using the

following formula :

Calculation :

Area of Sample Wt. of Std (2) 100

Assay = ------------------------ × --------------------- × Purity of Std × ------------------------------ × 0.7924
Av. Area of Std (2) Wt. of sample (as such basis) (100 – water of sample)

Take average of two results obtained % age variation of test should not be more than 1.0% and each result
must fall in specified limit

Note:
Montelukast sodium is light sensitive, so all samples and dilutions should be protected from light. The
amber colored glassware’s should be used for analysis.

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Sig. : Sig. : Sig. :

Designation : QC Officer Designation : Sr. QC Officer Designation : QC Manager

Date : Date : Date :