IPC/7035/IP-2010/AL-4
AMENDMENT LIST- 4 TO IP 2010
2.2.9. Microbial Contamination in Non Sterile Products. Page 37
Pre-treatment of the sample
Fatty products. Page 38-39, line 11
Insert the following after “not more than 30 minutes”
Adjust the volume to 100 ml with the same medium.
Preparation of the inoculum. Page 43
Microorganism used. Line 5
Change from: Shigella boydii
to: Shigella boydii ATCC 8700 or NCTC 12985
4.3. Indicators and Indicator Test Papers. Page 623
Insert before Bromocresol Purple
Bromocresol Green-Methyl Red Solution. Dissolve 0.15 g of bromocresol green and 0.1 g of methyl red in 180 ml
of absolute ethanol and dilute to 200 ml with water.
4.5. Volumetric Reagents and Solutions.
Perchloric acid, 0.1 M: Page 633, para 1, lines 7, 10 and 12
Change from: 0.5 per cent
to: 0.05 per cent
Amlodipine Tablets. Page 807
Related substances. Reference solution (a),
Change from: Reference solution (a). A solution containing 0.005 per cent w/v of amlodipine besilate RS in the
mobile phase.
to: Reference solution (a). A solution of amlodipine besilate RS containing 0.005 per cent w/v of
amlodipine in the mobile phase.
S-Amlodipine Besylate. Page 808
Structure and lines 1 to 4
Change to:
Cl
O
O H
H3CO
H3C
N
H
SO3H
O
O
CH3
,
,
2
1
H2O
2
NH2
C26H31ClN2O8S, 2.5H2O.
Mol. Wt. 612.1
S-Amlodipine
Besylate
is
(S)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester hemipentahydrate.
Related substances.
Change to: Related substances. Determine by liquid chromatography (2.4.14).
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Test solution. Dissolve about 100 mg of the substance under examination in 100.0 ml of the mobile phase. Dilute 5.0
ml of this solution to 100.0 ml with the mobile phase.
Reference solution. A 0.001 per cent w/v solution of S-amlodipine besylate RS in the mobile phase. Dilute 1.0 ml of
this solution to 100.0 ml with the mobile phase.
Use the chromatographic system as described in the Assay.
Inject the reference solution. The test is not valid unless the column efficiency is not less than 3000 theoretical plates
and tailing factor is not more than 2.0.
The relative retention time with respect to amlodipine for 3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2chlorophenyl)-6-methylpyridine-3,5-dicarboxylate (amlodipine impurity D) is about 0.5 and for benzene sulphonic
acid is about 0.14.
Inject the reference solution and the test solution. In the chromatogram obtained with the test solution the area of
any peak corresponding to amlodipine impurity D multiplied by 2 is not more than 1.5 times the area of the principal
peak in the chromatogram obtained with the reference solution (0.3 per cent) and sum of the areas of all the
secondary peaks is not more than 5 times the area of the principal peak in the chromatogram obtained with the
reference solution (1.0 per cent). Ignore any peak corresponding to benzene sulphonic acid.
Amphotericin B. Page 820
Assay. Lines 3 to 6
Change from: Weigh accurately about 60 mg, triturate with dimethylformamide and add, with shaking, sufficient
dimethylformamide to produce 100.0 ml. Dilute 10.0 ml to 100.0 ml with dimethylformamide.
to: Weigh accurately about 60 mg, triturate with dimethylsulphoxide and add, with shaking, sufficient
dimethylsuphoxide to produce 100.0 ml. Dilute 10.0 ml to 100.0 ml with dimethylsulphoxide.
Ampicillin Trihydrate. Page 2881
Related substances. Change to:
Related substances. Determine by liquid chromatography (2.4.14).
Note–Prepare the solutions immediately before use.
Test solution. Dissolve 31 mg of the substance under examination in mobile phase A and dilute to 10.0 ml with the
same solvent.
Reference solution (a). A 0.054 per cent w/v solution of anhydrous ampicillin RS in mobile phase A.
Reference solution (b). A 0.004 per cent w/v solution of cefradine RS in mobile phase A. To 5.0 ml of this solution,
add 5.0 ml of reference solution (a).
Reference solution (c). Dilute 1.0 ml of reference solution (a) to 20.0 ml with mobile phase A.
Chromatographic system
– a stainless steel column 25 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm),
– mobile phase: A. a mixture of 0.5 ml of dilute acetic acid, 50 ml of 0.2 M potassium dihydrogen phosphate
and 50 ml of acetonitrile, diluted to 1000 ml with water,
B. a mixture of 0.5 ml of dilute acetic acid, 50 ml of 0.2 M potassium dihydrogen phosphate
and 400 ml of acetonitrile, diluted to 1000 ml with water,
– a linear gradient programme using the conditions given below,
– flow rate: 1 ml per minute,
– spectrophotometer set at 254 nm,
– injection volume: 50 µl.
Time
(in min)
0 – tR
Mobile phase A
(per cent v/v)
85
Mobile phase B
(per cent v/v)
15
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tR – (tR + 30)
850
15100
(tR + 30)– (tR + 45)
0
100
(tR + 45)– (tR + 60)
85
15
tR is the retention time of ampicillin determined with reference solution (c).
Inject reference solution (b) with isocratic elution at the initial mobile phase composition to determine t R.
Inject reference solution (b). The test is not valid unless the resolution between the peaks due to ampicillin and
cefradine is not less than 3.0.
Inject reference solution (c) and the test solution. In the chromatogram obtained with the test solution, the area of
any secondary peak is not more than the area of the principal peak in the chromatogram obtained with reference
solution (c) (1.0 per cent).
Aspirin. Page 2882
Related substances. After chromatographic system, para 1, insert at the end.
The relative retention time with reference to acetylsalicylic acid for 4-hydroxybenzoic acid (aspirin impurity A) is
about 0.7; for 4-hydroxyisophthalic acid (aspirin impurity B) is about 0.8; for salicylic acid (aspirin impurity C) is
about 1.3; for acetylsalicylsalicylic acid (aspirin impurity D) is about 2.3; for salicylsalicylic acid (aspirin impurity
E) is about 3.2; for acetylsalicylic anhydride (aspirin impurity F) is about 6.0.
Para 2
Change to: Inject reference solution (a) and the test solution. Run the chromatogram 7 times the retention time of the
acetylsalicylic acid peak. In the chromatogram obtained with the test solution, the area of any peak corresponding to
aspirin impurities A, B, C, D, E and F is not more than 1.5 times the area of the principal peak in the chromatogram
obtained with reference solution (a) (0.15 per cent). The area of any other secondary peak is not more than 0.5 times
the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent). The sum of
areas of all the secondary peaks is not more than 2.5 times the area of the principal peak in the chromatogram
obtained with reference solution (a) (0.25 per cent). Ignore any peak with an area less than 0.3 times the area of the
principal peak in the chromatogram obtained with reference solution (a) (0.03 per cent).
Azithromycin.
Page 857
Related substances. After chromatographic system, para 1, insert at the end.
The relative retention time reference to azithromycin for azithromycin 3’- N-oxide (azithromycin impurity L) is
about 0.29; for 3’-(N,N-didemethyl)-3’-N-formylazithromycin (azithromycin impurity M) is about 0.37; for
aminoazithromycin (azithromycin impurity E) is about 0.43; for 3’-N-demethyl-3’-N- formylazithromycin
(azithromycin impurity F) is about 0.51; for 14-demethyl-14- (hydroxymethyl)azithromycin (azithromycin impurity
D) is about 0.54; for 13-O-decladinosylazithromycin (azithromycin impurity J) is about 0.54; for 3’-Ndemethylazithromycin (azithromycin impurity I) is about 0.61; for 3”-O-demethylazithromycin (azithromycin
impurity C) is about 0.73; for 3’-de(dimethylamino)-3’-oxoazithromycin (azithromycin impurity N) is about 0.76;
for 3’-N-[[4-(acetylamino)phenyl]sulfonyl]-3’-N-demethylazithromycin (azithromycin impurity H) is about 0.79;
for 6-demethylazithromycin (azithromycin impurity A) is about 0.83; for (azithromycin impurity P) is about 0.92;
for 2-desethyl-2-propylazithromycin (azithromycin impurity O) is about 1.23; for 3’-N-demethyl-3’-N-[(4methylphenyl)sulfonyl]azithromycin (azithromycin impurity
G) is about 1.26; for 3-deoxyazithromycin
(azithromycin impurity B) is about 1.31.
The correction factors for azithromycin impurity F is 0.3; for azithromycin impurity G is 0.2; for azithromycin
impurity H is 0.1; for azithromycin impurity L is 2.3; for azithromycin impurity M is 0.6 and for azithromycin
impurity N is 0.7.
Last para. Insert at the end
;ignore the peaks eluting before azithromycin impurity L and after azithromycin impurity B.
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Barium Sulphate. Page 872
Bulkiness. Delete the requirement
Compound Benzoic Acid Ointment. Page 887
Assay. Change to:
Assay. For benzoic acid – Weigh accurately about 2 g, dissolve in 150 ml of water, with the aid of gentle heat and
titrate with 0.1M sodium hydroxide using phenolphthalein solution as indicator. Reserve the solution for the Assay
for salicylic acid.
1 ml of 0.1 M sodium hydroxide, after deducting 1 ml for each 0.01381 g of C7H6O3 found in the Assay for salicylic
acid is equivalent to 0.01221 g of C7H6O2.
For salicylic acid - Cool the titrated solution obtained in the Assay for benzoic acid, dilute to 250.0 ml with water
and filter. To 5.0 ml of the filtrate add sufficient iron(III) nitrate solution to produce 50.0 ml. Filter, if necessary, to
remove haze and measure the absorbance of the resulting solution at the maximum at about 530 nm (2.4.7) using
iron(III) nitrate solution in the reference cell. Calculate the content of C7H6O3 from the absorbance obtained by
repeating the operation using 5 ml of a 0.024 per cent w/v solution of salicylic acid and beginning at the words 'add
sufficient iron(III) nitrate solution ...'.
Bupivacaine Injection. Page 934
Identification.
B. Delete the requirement
Change from: C.
to: B.
Assay. Change to:
Assay. Determine by liquid chromatography (2.4.14).
Test solution. Dilute a quantity of the injection with sufficient mobile phase to produce a solution containing 0.0025
per cent w/v of anhydrous bupivacaine hydrochloride.
Reference solution (a). A 0.0025 per cent w/v solution of bupivacaine hydrochloride RS in the mobile phase.
Reference solution (b). A 0.1 per cent w/v solution of 2,6-dimethylaniline in acetonitrile, dilute 10 volumes to 20
volumes with the mobile phase and then dilute 1 volume of the resulting solution to 100 volumes with reference
solution (a).
Chromatographic system
– a stainless steel column 30 cm x 3.9 mm, packed with octadecylsilane bonded to porous silica (10 µm), (Such
as µBondapak C18)
– mobile phase: a mixture of 40 volumes of 0.02M phosphate buffer pH 8.0 and 60 volumes of acetonitrile ,
– flow rate: 1 ml per minute,
– spectrophotometer set at 240 nm,
– injection volume: 20 µl.
Inject reference solution (b). The test is not valid unless the resolution between the peaks corresponding to
bupivacaine hydrochloride and 2,6-dimethylaniline is not less than 8.0.
Inject reference solution (a) and the test solution.
Calculate the content of C18H28N2O,HCl.
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IPC/7035/IP-2010/AL-4
Butylparaben. Page 942
Related substances. Change to:
Related substances. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 50 mg of the substance under examination in 2.5 ml of methanol and dilute to 50.0 ml
with the mobile phase. Dilute 10.0 ml of this solution to 100.0 ml with the mobile phase.
Reference solution (a). Dissolve 5 mg of 4-hydroxybenzoic acid, 5 mg of propyl parahydroxybenzoate
(butylparaben impurity D) and 5 mg of the substance under examination in the mobile phase and dilute to 100.0 ml
with the mobile phase. Dilute 1.0 ml of this solution to 10.0 ml with the mobile phase.
Reference solution (b). Dissolve 50 mg of butyl paraben RS in 2.5 ml of methanol and dilute to 50.0 ml with the
mobile phase. Dilute 10.0 ml of this solution to 100.0 ml with the mobile phase.
Reference solution (c). Dilute 1.0 ml of the test solution to 20.0 ml with the mobile phase. Dilute 1.0 ml of this
solution to 10.0 ml with the mobile phase.
Reference solution (d). Dissolve 5 mg of iso-butyl parahydroxybenzoate RS (butylparaben impurity E RS) in the
mobile phase and dilute to 100.0 ml with the mobile phase.
Reference solution (e). Dilute 0.5 ml of reference solution (d) to 50.0 ml with reference solution (b).
Chromatographic system
– a stainless steel column 15 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm),
– column temperature: 35°
– mobile phase: a mixture of 50 volumes of 0.68 per cent w/v solution of potassium dihydrogen phosphate, and
50 volumes of methanol,
– flow rate: 1.3 ml per minute,
– spectrophotometer set at 272 nm,
– injection volume: 10 µl.
The relative retention time with reference to butylparaben for 4-hydroxybenzoic acid is about 0.1, for butylparaben
impurity D is about 0.5 and for butylparaben impurity E is about 0.9.
Inject reference solution (a) and (e). The test is not valid unless the resolution between the peaks corresponding to
butylparaben and butylparaben impurity D is not less than 5.0 in the chromatogram obtained with reference solution
(a) and the resolution between the peaks corresponding to butylparaben and butylparaben impurity E is not less than
1.5 in the chromatogram obtained with reference solution (e).
Inject reference solution (c) and the test solution. Run the chromatogram 1.5 times the retention time of the principal
peak. In the chromatogram obtained with the test solution the area of any peak corresponding to 4-hydroxybenzoic
acid multiplied by 1.4 is not more than the area of the principal peak in the chromatogram obtained with reference
solution (c) (0.5 per cent). The area of any other secondary peak is not more than the area of the principal peak in the
chromatogram obtained with reference solution (c) (0.5 per cent). The sum of areas of all the secondary peaks is not
more than twice the area of the principal peak in the chromatogram obtained with reference solution (c) (1.0 per
cent). Ignore the peak with an area less than 0.2 times the area of the principal peak in the chromatogram obtained
with reference solution (c) (0.1 per cent).
Assay. Change to:
Assay. Determine by liquid chromatography (2.4.14), as described in the Related substances.
Inject reference solution (b) and the test solution.
Calculate the content of C11H14O3.
Cefaclor Oral Suspension. Page 995
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IPC/7035/IP-2010/AL-4
Usual Strengths.
Change from: 15 mg per 5 ml; 375 mg per 5 ml
to: 125 mg per 5 ml; 250 mg per 5 ml
Cefuroxime Axetil. Page 1026
Related substances. Change to:
Related substances. Determine by liquid chromatography (2.4.14).
NOTE – Prepare the solutions immediately before use.
Test solution. Dissolve 10 mg of the substance under examination in the mobile phase and dilute to 50.0 ml with the
mobile phase.
Reference solution (a). Dilute 1.0 ml of the test solution to 100.0 ml with the mobile phase.
Reference solution (b). Heat 5 ml of the test solution at 60º for one hour to generate the D3-isomers.
Reference solution (c) Expose 5 ml of the test solution to ultraviolet light at 254 nm for 24 hours to generate Eisomers.
Reference solution (d). A 0.02 per cent w/v solution of cefuroxime axetil RS in the mobile phase.
Chromatographic system
– a stainless steel column 25 cm × 4.6 mm, packed with trimethylsilane bonded to porous silica (5 µm),
– mobile phase: a mixture of 38 volumes of methanol and 62 volumes of a 2.3 per cent solution of ammonium
dihydrogen phosphate,
– flow rate: 1 ml per minute,
– spectrophotometer set at 278 nm,
– injection volume: 20 µl.
The relative retention times with respect to cefuroxime axetil diastereoisomer A for cefuroxime axetil
diastereoisomer B is about 0.9, for cefuroxime axetil D3-isomers is about 1.2 and for E-isomers is about 1.7 and 2.1.
Inject reference solution (b). The test is not valid unless the resolution between the peaks corresponding to
cefuroxime axetil diastereoisomer A and cefuroxime axetil D3-isomer is not less than 1.5.
Inject reference solutions (a), (b), (c) and the test solution. In the chromatogram obtained with the test solution, the
area of the peak corresponding to cefuroxime axetil D3-isomers is not more than 1.5 times the sum of the area of the
principal peaks in the chromatogram obtained with reference solution (a) (1.5 per cent), the area of peak
corresponding to cefuroxime axetil E-isomers is not more than the sum of the area of the principal peaks in the
chromatogram obtained with reference solution (a) (1.0 per cent). The area of any other secondary peak is not more
than 0.5 times the sum of the area of the principal peaks in the chromatogram obtained with reference solution (a)
(0.5 per cent) and sum of all the secondary peaks is not more than 3 times the sum of the area of the principal peaks
in the chromatogram obtained with reference solution (a) (3.0 per cent). Ignore any peak with an area less than 0.05
times the sum of the area of the principal peaks in the chromatogram obtained with reference solution (a) (0.05 per
cent).
Assay. Change to:
Assay. Determine by liquid chromatography (2.4.14).
Use chromatographic system, test solution and reference solution (d), as described in the Related substances.
Inject reference solution (d). The test is not valid unless the resolution between the peaks corresponding to
cefuroxime axetil diastereoisomers A and B is not less than 1.5 and the relative standard deviation for replicate
injections for the sum of diastereomer A and B peaks is not more than 2.0 per cent.
Inject reference solution (d) and the test solution.
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Calculate the content of C16H16N4O8S as the sum of areas of the two diastereoisomer peaks.
1 mg of C20H22N4O10S is equivalent to 0.8313 mg of C16H16N4O8S.
Cephalexin. Page 1031
Para 2, line 2
Change from: 101.0 per cent
to: 102.0 per cent
Light absorption. Delete the requirement
Cholecalciferol Tablets. Page 2896
Usual strengths
Change from: 0.25 µg; 1 µg
to: 0.25 mg; 1 mg
Ciclesonide Inhalation. Page 1083
Assay. Chromatographic system. last line
Change from: 200 µl
to: 100 µl
Clarithromycin. Page 1101
Related substances. Last para
Change to: The relative retention time with reference to clarithromycin for 3-O-decladinosyl-6-Omethylerythromycin A (clarithromycin impurity I) is about 0.38; for 2-demethyl-2-(hydroxymethyl)-6-Omethylerythromycin A (clarithromycin impurity A) is about 0.42; for erythromycin A (E)-9-oxime (clarithromycin
impurity J) is about 0.63; for 6-O-methylerythromycin A (Z)-9-oxime (clarithromycin impurity L) is about 0.74; for
6-O-methyl-15-norerythromycin A (clarithromycin impurity B) is about 0.79; for 3”-N-demethyl-6-Omethylerythromycin A (E)-9- oxime (clarithromycin impurity M) is about 0.81; for 6-O-methylerythromycin A (E)9-oxime (clarithromycin impurity C) is about 0.89; for 3”-N-demethyl-6-O-methylerythromycin A (clarithromycin
impurity D) is about 0.96; for (10E)-10,11-didehydro-11-deoxy-6-O-methylerythromycin A (clarithromycin
impurity N) is about 1.15; for 6,11-di-O-methylerythromycin A (clarithromycin impurity E) is about 1.27; for 6,12di-O-methylerythromycin A (clarithromycin impurity F) is about 1.33; for 4’,6-di-O-methylerythromycin A
(clarithromycin impurity P) is about 1.35; for 6-O-methylerythromycin A (Z)-9-(O-methyloxime) (clarithromycin
impurity O) is about 1.41; for (1S,2R,5R,6S,7S,8R,9R,11Z)-2-ethyl-6-hydroxy-9-methoxy-1,5,7,9,11,13hexamethyl-8-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-3,15oxabicyclo[10.2.1]pentadeca-11,13-dien-4-one (3-O-decladinosyl-8,9:10,11- dianhydro-6-O-methylerythromycin A9,12-hemiketal (clarithromycin impurity K) is about 1.59; for 6-O-methylerythromycin A (E)-9-(O-methyloxime)
(clarithromycin impurity G) is about 1.72; for 3”-N-demethyl-3’-N-formyl-6-O-methylerythromycin
A
(clarithromycin impurity H) is about 1.82. The correction factor of clarithromycin impurity G is 0.27 and
clarithromycin impurity H is 0.15.
Inject reference solution (b) and the test solution. In the chromatogram obtained with the test solution, the area of
any secondary peak is not more than the area of the peak in the chromatogram obtained with reference solution (b)
(1.0 per cent) and the sum of areas of all the secondary peaks is not more than 3.5 times the area of the peak in the
chromatogram obtained with reference solution (b) (3.5 per cent).
Clomipramine Capsules. Page 1111
Assay.
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IPC/7035/IP-2010/AL-4
Reference solution.
Change to: Reference solution. A 0.005 per cent w/v solution of clomipramine RS in methanol.
Last line
Change from: C16H13ClN2O2
to: C19H23ClN2,HCl
Clopidogrel Tablets. Page 1119
Related substances. Last para, line 9
Change from: twice
to: 0.75 times
Absorbent Cotton. Page 1137
Surface-active substances. Lines 6 and 7
Change from: After 5 minutes, the height of the froth does not exceed 2 mm above the surface of the liquid.
to: After 5 minutes, any foam present must not cover the entire surface of the liquid.
Water-soluble substances. Lines 6, 7 and 8
Change from: Evaporate 400 ml of the filtrate and dry the residue to constant weight at 105°.
to: Evaporate 400 ml of the filtrate (corresponding to 4/5 of the mass of the sample taken) and dry the
residue to constant weight at 105°.
Crospovidone. Page 1141
Vinylpyrrolidinone: Delete the requirement
Diclofenac Tablets. Page 2900
Assay. Test solution
Change to: Test solution. Weigh and powder 20 tablets. Disperse a quantity of the powder containing about 50 mg
of Diclofenac Sodium in 100.0 ml of the mobile phase and filter. Dilute 5.0 ml of the solution to 50.0 ml with the
mobile phase.
Diphenhydramine Hydrochloride. Page 1232
Related substances. Change to:
Related substances. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 70 mg of the substance under examination in 20.0 ml of the mobile phase. Dilute 2.0 ml of
this solution to 10.0 ml with the mobile phase.
Reference solution (a). Dilute 1.0 ml of the test solution to 10.0 ml with the mobile phase. Dilute 1.0 ml of this
solution to 20.0 ml with the mobile phase.
Reference solution (b). Dissolve 5 mg of 2-(diphenylmethoxy)-N-methylethanamine RS (diphenhydramine impurity
A RS) in the mobile phase and dilute to 10.0 ml with the mobile phase. To 2.0 ml of this solution add 1.5 ml of the
test solution and dilute to 10.0 ml with the mobile phase.
Chromatographic system
– a stainless steel column 25 cm x 4.6 mm, packed with endcapped octylsilane bonded to porous silica (5 µm),
– mobile phase: a mixture of 35 volumes of acetonitrile and 65 volumes of 0.54 per cent w/v solution of
potassium dihydrogen phosphate previously adjusted to pH 3.0 with orthophosphoric acid,
– flow rate: 1.2 ml per minute,
– spectrophotometer set at 220 nm,
– injection volume: 10 µl.
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The relative retention time with reference to diphenhydramine (retention time is about 6 minutes) for
diphenhydramine impurity A is about 0.9, for 2-[(RS)-(4-methylphenyl)phenylmethoxy]-N,N- dimethylethanamine
(diphenhydramine impurity B) is about 1.5, for 2-[(RS)-(4-bromophenyl)phenylmethoxy]-N,N- dimethylethanamine
(diphenhydramine impurity C) is about 1.8, for benzhydrol (diphenhydramine impurity D) is about 2.6 and for
benzophenone (diphenhydramine impurity E) is about 5.1. The correction factor for diphenhydramine impurity D is
0.7.
Inject reference solution (b). The test is not valid unless the resolution between the peaks corresponding to
diphenhydramine and diphenhydramine impurity A is not less than 2.0.
Inject reference solution (a) and the test solution. Run the chromatogram seven times the retention time of the
principal peak. In the chromatogram obtained with the test solution the area of peak due to diphenhydramine
impurity A is not more than the area the principal peak in the chromatogram obtained with reference solution (a)
(0.5 per cent). The area of any secondary peak is not more than 0.6 times the area of the principal peak in the
chromatogram obtained with reference solution (a) (0.3 per cent). The sum of areas of all the secondary peaks is not
more than twice the area of the principal peak in the chromatogram obtained with reference solution (a) (1.0 per
cent). Ignore any peak with an area less than 0.1 times the area of the principal peak in the chromatogram obtained
with reference solution (a) (0.05 per cent).
Fenofibrate Capsules. Page 2912
Dissolution (2.5.2).
Test solution. Change to:
Test solution. Dilute the filtrate if necessary, with the dissolution medium.
Reference solution. Change to:
Reference solution. Dissolve an accurately weighted quantity of fenofibrate RS in mobile phase and dilute with
mobile phase to obtain a solution having a known concentration similar to the expected concentration of test
solution.
Assay. Chromatograhic system, line 5
Change from: 136 g
to: 136 mg
Fluconazole. Page 2913
Related substances. Lines 10 and 11
Change from: The correction factor of fluconazole impurity A is 12.5, fluconazole impurity B is 0.78 and
fluconazole impurity C is 20.
to: The correction factor of fluconazole impurity A is 0.08, for fluconazole impurity B is 1.29 and for
fluconazole impurity C is 0.05.
Fluticasone Propionate Inhalation. Page 1383
Assay. Chromatographic system. last line
Change from: 200 µl
to: 100 µl
Fluticasone Propionate Powder for Inhalation. Page 1383
Assay. Chromatographic system. last line
Change from: 200 µl
to: 100 µl
Fumaric Acid. Page 1394
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Insert before Identification.
Description. A white, odourless granules or crystalline powder.
Identification
Change to: Determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained
with fumaric acid RS or with the reference spectrum of fumaric acid.
Heavy metals. Para 2, line 8
Change from: lead standard solution (1 ppm)
to: lead standard solution (10 ppm)
Maleic acid. Change to:
Maleic acid. Not more than 0.1 per cent.
Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 100 mg of the substance under examination in 100.0 ml of the mobile phase.
Reference solution (a). A 0.0001 per cent w/v solution of maleic acid RS in the mobile phase.
Reference solution (b). A 0.001 per cent w/v solution of fumaric acid RS and 0.0005 per cent w/v solution of maleic
acid RS in the mobile phase.
Chromatographic system
– a stainless steel column 22 cm x 4.6 mm, strong cation-exchange resin consisting of sulfonated cross-linked
styrene-divinylbenzene copolymer in the hydrogen form (7 to 11µm),
– mobile phase. 0.0025 M sulphuric acid,
– flow rate: 0.3 ml per minute,
– spectrophotometer set at 210 nm,
– injection volume: 5 µl.
Inject reference solution (b) and reference solution (a).The test is not valid unless the resolution obtained with
reference solution (b), between the peaks corresponding to maleic acid and fumaric acid is not less than 2.5 and
relative standard deviation for replicate injections obtained with reference solution (a) is not more than 2.0 per cent.
The relative retention time with reference to fumaric acid for maleic acid is about 0.5.
Inject reference solution (a) and the test solution.
Calculate the content of maleic acid, C4H4O4.
Glibenclamide Tablets.
Page 1415
Identification. A
Change to: In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to that
in the chromatogram obtained with the reference solution.
Uniformity of content. Change to:
Uniformity of content. Complies with the test stated under Tablets.
Determine by liquid chromatography (2.4.14), as described under Assay using the following test solution.
Test solution. Disperse one tablet in a mixture of 2 ml of water and 20 ml of methanol, mix with the aid of
ultrasound until fully dispersed and filter.
Glimepiride Tablets. Page 1419
Related substances. After chromatograhic system, para 1,
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Insert at the end.
The correction factor for glimepiride impurity B is 0.77.
Griseofulvin Tablets. Page 1428
Assay. Line 3
Change from: add 60 ml of ethyl acetate
to: add 60 ml of ethyl acetate, heat at 60° with shaking for 20 minutes. Allow to cool and dilute to 100.0
ml with ethyl acetate.
Ipratropium Powder for Inhalation.
Page 2921
Related substances.
Insert the following.
A. Determine by thin-layer chromatography (2.4.17), coating the plate with silica gel GF 254.
Mobile phase. A mixture of 1 volume of formic acid, 3 volumes of water, 18 volumes of ethanol and 18 volumes of
dichloromethane.
Test solution. Shake a quantity of the contents of the capsules containing about 0.1 g of Ipratropium Bromide with 1
ml of methanol for 2 minutes, centrifuge and use the supernatant.
Reference solution (a). Dilute 1 volume of the test solution to 200 volumes with a saturated solution of glucose.
Reference solution (b). A 0.0005 per cent w/v solution of tropic acid in a saturated solution of glucose.
Apply to the plate 10 µl of each solution. After development, dry the plate at 60° for 15 minutes, spray with
potassium iodobismuthate solution, dry briefly in a current of air and spray with a 5.0 per cent w/v solution of
sodium nitrite. In the chromatogram obtained with the test solution any spot corresponding to tropic acid is not more
intense than the spot in the chromatogram obtained with reference solution (a) 0.5 per cent); any other secondary
spot is not more intense than the spot in the chromatogram obtained with reference solution (a) (0.5 per cent).
Change from: Determine by liquid chromatography. to: B. Determine by liquid chromatography.
Isosorbide Dinitrate Tablets. Page 1522
Uniformity of content. Change to:
Uniformity of content. Complies with the test stated under Tablets.
Determine by liquid chromatography (2.4.14), as described in the Assay using following modifications.
Test solution. Disperse 1 tablet in 20 ml of the mobile phase and dilute to obtain a concentration of 0.005 per cent
w/v of isosorbide dinitrate in the same solvent.
Reference solution. A 0.005 per cent w/v solution of isosorbide dinitrate RS in the mobile phase.
Inject the reference solution and the test solution.
Calculate the content of C6H8N2O8.
Diluted Isosorbide Mononitrate. Page 1524
Para 3, line 2
Change from: 105.0 per cent of C6H9NO6
to: 105.0 per cent of the stated amount of C6H9NO6
Isosorbide Mononitrate Tablets. Page 1525
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Uniformity of content. Change to:
Uniformity of content. Complies with the test stated under Tablets.
Determine by liquid chromatography (2.4.14), as described in the Assay using following modification.
Test solution. Disperse 1 tablet in 20 ml of the mobile phase and dilute to obtain a concentration of 0.005 per cent
w/v of isosorbide mononitrate in the same solvent.
Reference solution. A 0.005 per cent w/v solution of isosorbide mononitrate RS in the mobile phase.
Inject the reference solution and the test solution.
Calculate the content of C6H9NO6 in the tablet.
Ketorolac Tromethamine. Page 1543
Related substances. Chromatographic system, line 2
Change from: octadecylsilane
to: octylsilane
Lamotrigine Sustained-release Tablets.
Page 1567
Related substances.
Change to: Related substances. Determine by liquid chromatography (2.4.14).
Solvent mixture. 60 volumes of methanol and 40 volumes of water.
Test solution. Weigh and transfer 5 tablets in to suitable volumetric flask, add methanol to 10 per cent of the volume
of the flask and sonicate to disperse. Further add solvent mixture to 75 per cent of the volume of the flask and
sonicate for 60 minutes in cool water with occasional shaking. Make up the volume with the solvent mixture.
Centrifuge and dilute the supernatant liquid with the solvent mixture to prepare a 0.01per cent w/v solution.
Reference solution. A 0.0001 per cent w/v solution of lamotrigine RS, dissolved in minimum quantity of methanol,
and diluted with the solvent mixture.
Chromatographic system
– a stainless steel column 25 cm x 4.6 mm, packed with octadecylsilane chemically bonded to porous silica (5 µm),
– mobile phase: a mixture of 60 volumes of water, 40 volumes of methanol and 0.01 volumes of triethylamine,
adjusted to pH 7.0 with 10 per cent v/v solution of orthophosphoric acid,
– flow rate. 1 ml per minute,
– spectrophotometer set at 309 nm,
– injection volume. 20 µl.
Inject the reference solution. The test is not valid unless the column efficiency is not less than 3000 theoretical plates
and the tailing factor is not more than 2.0.
Inject the reference solution and the test solution. In the chromatogram obtained with the test solution, the area of
any secondary peak is not more than 0.5 times the area of the peak in the chromatogram obtained with the reference
solution (0.5 per cent) and sum of the areas of all the secondary peaks is not more than 1.5 times the area of the peak
in the chromatogram obtained with the reference solution (1.5 per cent).
Levodopa and Carbidopa Tablets. Page 1576
Assay. Reference solution, line 3
Change from: 2 ml
to: 50 ml
Losartan Potassium and Amlodipine Tablets. Page 2927
Dissolution. Reference solution. line 2
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Change from: 0.025 per cent
to: 0.035 per cent
Mefloquine Tablets. Page 2931
Dissolution. Lines 9 and 10
Change from: mefloquine hydrochloride RS in the same medium.
to: mefloquine hydrochloride RS, prepared by dissolving in minimum quantity of methanol and diluting
with the dissolution medium.
Melphalan Injection. Page 1647
Para 2
Change to: The inection is prepared immediately before use by dissolving the contents of the sealed container which
contains Melphalan Hydrochloride with or without auxillary substances in a suitable solvent and then diluting with
the requisite volume of a suitable diluent in accordance with the manufacturer’s instructions.
Insert before Appearance of solution
Tests
Dissolve the contents of one container in a suitable solvent, dilute the requisite volume of a suitable diluent in
accordance with the manufacturer’s instruction to produce a final solution containing 0.5 per cent w/v of anhydrous
melphalan and allow to stand for 30 minutes (Solution A).
Appearance of solution
Change to: Appearance of solution. Solution A is not more opalescent than opalescence standard OS2 (2.4.1).
pH
Change to: pH (2.4.24). 6.0 to 7.0, determined in solution A.
Ionisable chlorine. Delete the requirement.
Meropenem Injection.
Page 1656
Insert before Bacterial endotoxins
Sodium carbonate. Weigh accurately a quantity of the injection containing about 50 mg of anhydrous meropenem
and dissolve in sufficient water to produce 100.0 ml. Dilute the resulting solution appropriately with water and
determine by Method A for flame photometry (2.4.4), measuring at 589 nm or by Method A for atomic absorption
spectrophotometry (2.4.2), using sodium solution FP, suitably diluted with water for the reference solutions.
1 g of Na is equivalent to 2.305 g of Na2CO3.
Methylparaben. Page 1672
Assay. Change to:
Assay. Determine by liquid chromatography (2.4.14), as described in the Related substances. (Amendment list-3)
Inject reference solution (b) and the test solution.
Calculate the content of C8H8O3.
Mometasone Furoate. Page 1700
Related substances. Reference solution (b), line 2
Change from: 25.0 ml
to: 20.0 ml
Loss on drying. Line 2
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Change from: 1.0 g
to: 1.0 g by drying in an oven at 105°.
Naproxen Sustained-release Tablets. Page 1757
Insert before Para 1
Naproxen Sustained-release Tablets manufactured by different manufacturers, whilst complying with the
requirements of the monograph, are not interchangeable.
Dissolution. Change to:
Dissolution (2.5.2). Complies with the test stated under tablets.
Nevirapine Tablets. Page 1772
Identification. A
Change to: When examined in the range 200 nm to 400 nm (2.4.7) a 0.001 per cent w/v solution in methanol, shows
an absorption maximum at about 283 nm.
Nifedipine. Page 2935
Related substances. Last para, lines 11 and 12
Change from: reference solution (d)
to: reference solution (d) (0.2 per cent)
Omeprazole. Page 1813
Identification. C
Change to: In the test for Related substances, the principal peak in the chromatogram obtained with the test solution
corresponds to the principal peak in the chromatogram obtained with reference solution (a).
Omeprazole Capsules. Page 1814
Assay. Reference solution (b).
Change to: Reference solution (b).Take 20 mg of omeprazole RS in 100-ml volumetric flask, add 20.0 ml of 0.1 M
sodium hydroxide, shake vigorously for 5 minutes and dilute to volume with 0.1 M sodium hydroxide. Dilute 5.0 ml
of this solution with the mobile phase to produce 50.0 ml.
Ondansetron Orally Disintegrating Tablets. Page 1816
Related substances. Reference solution (e), line 1
Change from: reference solution (c)
to: reference solution (d)
Insert before Water.
Uniformity of content. Complies with the test stated under Tablets.
Carry out the procedure described under Assay but using the following test solution.
Test solution. Disperse 1 tablet in 0.01 M hydrochloric acid and dilute to 100.0 ml with the same solvent and filter.
Calculate the content of C18H19N3O in the tablet.
Ondansetron Oral Solution.
Page 1818
Related substances: Change to:
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Related substances. Determined by liquid chromatography (2.4.14), as described in the Assay with the following
modifications.
Test solution. Weigh accurately a quantity of oral solution containing about 5 mg of Ondansetron Hydrochloride in
50-ml volumetric flask, dissolve and dilute with the mobile phase and mix.
Inject reference solution (c). The test is not valid unless the resolution between ondansetron impurity A and
ondansetron is not less than 1.5. The relative retention time with reference to ondansetron for ondansetron impurity
D is about 0.34, for imidazole is about 0.4, for 2-methyl imidazole is about 0.53, for des-C-methyl ondansetron
hydrochloride is about 0.62, for N-desmethyl ondansetron maleate is about 0.83, for ondansetron impurity A is about
1.2.
Inject reference solution (b). The test is not valid unless the tailing factor is not more than 2.0 and the relative
standard deviation for replicate injections is not more than 2.0 per cent.
Inject reference solution (b) and the test solution. In the chromatogram obtained with the test solution, the area of
any peak corresponding to imidazole, 2-methyl imidazole, des-(-methyl) ondansetron hydrochloride, N- desmethyl
ondansetron maleate, ondansetron impurity A is not more than 0.2 times the area of the principal peak in the
chromatogram obtained with reference solution (b) (0.2 per cent). The area of any other secondary peak is not more
than 0.2 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent)
and sum of all the secondary peaks is not more than 0.5 times the area of the principal peak in the chromatogram
obtained with reference solution (b) (0.5 per cent).
Oxcarbazepine. Page 1832
Category.
Change from: Non-opioid analgesics
to: Category. Anticonvulsants
Oxytocin. Page 1842
Insert before Category
By convention, for the purpose of labeling oxytocin preparations, 1 mg of oxytocin peptide (C43H66O12S2) is
equivalent to 600 IU of biological activity.
Assay. Last line
Change from: Calculate the content of C43H66O12S2.
to: Calculate the units of the oxytocic activity or the potency.
Potassium Clavulanate. Page 1937
Category.
Change from: Antibacterial
to: Beta-lactamase inhibitor
Potassium Clavulanate Diluted. Page 1938
Category.
Change from: Antibacterial
to: Beta-lactamase inhibitor
Related substances.
Insert before Test solution.
NOTE – Prepare the solutions immediately before use.
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Chromatographic system, line 1
Change from: 25 cm
to: 10 cm
Insert after line 2
– column temperature: 40°,
Last para, Change to:
Inject reference solution (a) and the test solution. In the chromatogram obtained with the test solution, the area of
any secondary peak is not more than the area of the principal peak in the chromatogram obtained with reference
solution (a) (1.0 per cent) and the sum of areas of all the secondary peaks is not more than 2 times the area of the
principal peak in the chromatogram obtained with the reference solution (a) (2.0 per cent). Ignore any peak with an
area less than 0.05 times the area of the principal peak in the chromatogram obtained with reference solution (a)
(0.05 per cent).
Prednisolone Tablets. Page 1952
Dissolution. Line 9
Change from: prednisolone RS.
to: prednisolone RS prepared by dissolving in methanol and diluting with the dissolution medium.
Propylparaben. Page 1991
Assay. Change to:
Assay. Determine by liquid chromatography (2.4.14) as described in the Related substances. (Amendment list 3)
Inject reference solution (b) and the test solution.
Calculate the content of C10H12O3.
Ranitidine Hydrochloride. Page 2043
Identification. B
Change to: In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to that
in the chromatogram obtained with the reference solution.
Related substances. Page 2947
After chromatographic system, insert before para 1,
The relative retention time with reference to ranitidine for N-methyl-2-nitroacetamide (ranitidine impurity H) is
about 0.1; for 3-(methylamino)-5,6-dihydro-2H-1,4-thiazin-2-one-oxime (ranitidine impurity G) is about 0.2; for [5[(dimethylamino)methyl]furan-2-yl]methanol (ranitidine
impurity F) is about 0.4; for 2-[[[5[(dimethylamino)methyl]furan-2- yl]methyl]sulfanyl]ethanamine (ranitidine impurity B) is about 0.5; for N-[2-[[[5[(dimethylamino)methyl]furan-2-yl]methyl]sulfinyl]ethyl]-N’-methyl-2-nitroethene-1,1-diamine (ranitidine impurity
C) is about 0.6; for N-[2-[[[5-[(dimethyloxidoamino)methyl]furan-2-yl]methyl]sulfanyl]ethyl]-N’- methyl-2nitroethene-1,1-diamine (ranitidine impurity E) is about 0.7; for N-[2-[[[5-[(dimethylamino)methyl]furan-2yl]methyl]sulfanyl]ethyl]-2-nitroacetamide
(ranitidine
impurity
D)
is
about
0.8;
for
1,1’-N[methylenebis(sulfanediylethylene)]bis(N’-methyl-2-nitroethene-1,1- diamine) (ranitidine impurity J) is about 0.9;
for
2,2’-methylenebis[N-[2-[[[5-[(dimethylamino)methyl]furan-2-yl]methyl]sulfanyl]ethyl]-N’-methyl-2nitroethene-1,1-diamine] (ranitidine impurity I) is about 1.3; for N,N’-bis[2-[[[5-[(dimethylamino)methyl]furan-2yl]methyl]sulfanyl]ethyl]-2- nitroethene-1,1-diamine (ranitidine impurity A) is about 1.7. The correction factor for
ranitidine impurity J is 2.0.
Para 2,
Change to: Inject reference solution (a) and the test solution. In the chromatogram obtained with the test solution,
the area of any peak corresponding to ranitidine impurity A is not more than 0.5 times the area of the principal peak
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in the chromatogram obtained with reference solution (a) (0.5 per cent). The area of any other identified peak is not
more than 0.2 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per
cent). The area of any other secondary peak is not more than 0.1 times the area of the principal peak in the
chromatogram obtained with reference solution (a) (0.1 per cent) and the sum of the area of all the secondary peaks
other than ranitidine impurity A is not more than 0.5 times the area of the principal peak in the chromatogram
obtained with reference solution (a) (0.5 per cent). Ignore any peak with an area less than 0.05 times the principal
peak in the chromatogram obtained with the reference solution (a) (0.05 per cent).
Secnidazole. Page 2095
Related substances. After chromatographic system, para 1, line 2
Change from: 2-methyl-4-nitroimidazole
to: 2-methyl-5-nitroimidazole
Water.
Change from: 4.0 to 5.0 per cent,
to: 4.0 to 6.0 per cent.
Sodium Metabisulphite. Page 2132
Identification. Change to:
A. A 5 per cent w/v solution in carbon dioxide free water (solution A) gives reaction A of sodium salts (2.3.1).
B. To 0.4 ml of iodinated potassium iodide solution, add 8 ml of water and 1 ml of solution A, diluted 1 to
10 in water. The solution is colourless and gives reaction (a) of sulphates (2.3.1).
Acidity. Change to:
pH (2.4.24). 3.5 to 5.0, determined in solution A.
Sodium Methylparaben. Page 2132
Related substances. Change to:
Related substances. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 50 mg of the substance under examination in 2.5 ml of methanol and dilute to 50.0 ml with
the mobile phase. Dilute 10.0 ml of this solution to 100.0 ml with the mobile phase.
Reference solution (a). Dissolve 5 mg of 4-hydroxybenzoic acid and 5 mg of the substance under examination in
the mobile phase and dilute to 100.0 ml with the mobile phase. Dilute 1.0 ml of this solution to 10.0 ml with the
mobile phase.
Reference solution (b). Dissolve 50 mg of methylparaben RS in 2.5 ml of methanol and dilute to 50.0 ml with the
mobile phase. Dilute 10.0 ml of this solution to 100.0 ml with the mobile phase.
Reference solution (c). Dilute 1.0 ml of the test solution to 20.0 ml with the mobile phase. Dilute 1.0 ml of this
solution to 10.0 ml with the mobile phase.
Chromatographic system
– a stainless steel column 15 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm),
– mobile phase: a mixture of 35 volumes of 0.68 per cent w/v solution of potassium dihydrogen phosphate, and
65 volumes of methanol,
– flow rate: 1.3 ml per minute,
– spectrophotometer set at 272 nm,
– injection volume: 10 µl.
The relative retention time with reference to methyparaben for 4-hydroxybenzoic acid is about 0.6.
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Inject reference solution (a). The test is not valid unless the resolution between the peaks due to methylparaben and
4-hydroxybenzoic acid is not less than 2.0.
Inject reference solution (c) and the test solution. Run the chromatogram five times the retention time of the
principal peak. In the chromatogram obtained with the test solution the area of any peak corresponding to 4hydroxybenzoic acid multiplied by 1.4 is not more than the six times the area of the principal peak in the
chromatogram obtained with reference solution (c) (3.0 per cent). The area of any other secondary peak is not more
than the area of the principal peak in the chromatogram obtained with reference solution (c) (0.5 per cent). The sum
of areas of all the secondary peaks other than 4-hydroxybenzoic acid is not more than twice the area of the principal
peak in the chromatogram obtained with reference solution (c) (1.0 per cent). Ignore the peak with an area less than
0.2 times the area of the principal peak in the chromatogram obtained with reference solution (c) (0.1 per cent).
Assay. Change to:
Assay. Determine by liquid chromatography (2.4.14), as described in the Related substances.
Inject reference solution (b) and the test solution.
Calculate the content of C8H7NaO3, multiplying the content of methylparaben by a correction factor of 1.145.
Sodium Propylparaben. Page 2134
Related substances. Change to:
Related substances. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 50 mg of the substance under examination in 2.5 ml of methanol and dilute to 50.0 ml
with the mobile phase. Dilute 10.0 ml of this solution to 100.0 ml with the mobile phase.
Reference solution (a). Dissolve 5 mg of 4-hydroxybenzoic acid, 5 mg of ethyl parahydroxybenzoate RS
(propylparaben impurity C RS) and 5 mg of the substance under examination in the mobile phase and dilute to 100.0
ml with the mobile phase. Dilute 1.0 ml of this solution to 10.0 ml with the mobile phase.
Reference solution (b). Dissolve 50 mg of propylparaben RS in 2.5 ml of methanol and dilute to 50.0 ml with the
mobile phase. Dilute 10.0 ml of this solution to 100.0 ml with the mobile phase.
Reference solution (c). Dilute 1.0 ml of the test solution to 20.0 ml with the mobile phase. Dilute 1.0 ml of this
solution to 10.0 ml with the mobile phase.
Chromatographic system
– a stainless steel column 15 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm),
– mobile phase: a mixture of 35 volumes of 0.68 per cent w/v solution of potassium dihydrogen phosphate, and
65 volumes of methanol,
– flow rate: 1.3 ml per minute,
– spectrophotometer set at 272 nm,
– injection volume: 10 µl.
The relative retention time with reference to propylparaben for 4-hydroxybenzoic acid is about 0.3, for
propylparaben impurity C is about 0.7.
Inject reference solution (a). The test is not valid unless the resolution between the peaks due to propylparaben and
propylparaben impurity C is not less than 5.0.
Inject reference solution (c) and the test solution. Run the chromatogram 2.5 times the retention time of the principal
peak. In the chromatogram obtained with the test solution the area of any peak corresponding to 4-hydroxybenzoic
acid multiplied by 1.4 is not more than 8 times the area the principal peak in the chromatogram obtained with
reference solution (c) (4.0 per cent). The area of any other secondary peak is not more than the area of the principal
peak in the chromatogram obtained with reference solution (c) (0.5 per cent). The sum of areas of all the secondary
peaks other than 4-hydroxybenzoic acid is not more than twice the area of the principal peak in the chromatogram
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IPC/7035/IP-2010/AL-4
obtained with reference solution (c) (1.0 per cent). Ignore the peak with an area less than 0.2 times the area of the
principal peak in the chromatogram obtained with reference solution (c) (0.1 per cent).
Assay. Change to:
Assay. Determine by liquid chromatography (2.4.14), as described in the Related substances.
Inject reference solution (b) and the test solution.
Calculate the content of C10H11NaO3, multiplying the content of propylparaben by a correction factor of 1.122.
Sorbitol Solution (70 per cent) (Crystallising). Page 2955
Lead. Reference solution (a), (b) and (c). Line 2.
Change from: solvent mixture
to: the test solution
Assay. Last line
Change from: D-sorbitol
to: D-sorbitol (D-glucitol)
Sorbitol Solution (70 per cent) (Non-Crystallising). Page 2956
Lead. Reference solution (a), (b) and (c). Line 2.
Change from: solvent mixture
to: the test solution
Assay. Last line
Change from: D-sorbitol
to: D-sorbitol (D-glucitol)
Stearic Acid. Page 2958
Assay. Last line
Change from: Calculate the content of stearic acid
to: Calculate the content of stearic acid and palmitic acid.
Stearyl Alcohol. Page 2155
Assay. After chromatograhic system, para 1
Insert at the end.
and the relative standard deviation for replicate injections is not more than 1.5 per cent.
Sumatriptan. Page 2173
Related substances. Chromatographic system, lines 4 to 9
Change to: mobile phase: a mixture of 25 volumes of acetonitrile and 75 volumes of buffer solution prepared by
dissolving 0.97 g of dibutylamine, 0.735 g of orthophosphoric acid and 2.93 g of sodium dihydrogen phosphate in
750 ml of water, adjusted to pH 6.5 with sodium hydroxide solution and diluted to 1000 ml with water.
Thyroxine Tablets. Page 2222
Usual strength. Change to:
Usual strengths. 12.5 µg; 25 µg; 50 µg; 75 µg; 100 µg
Uniformity of content. Change to:
Uniformity of content. Comply with the test stated under Tablets.
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Determine by liquid chromatography (2.4.14), as described in the Assay, using the following solutions.
Test solution. To one tablet, add 10 ml of solvent mixture and shake for about 30 minutes, dilute with solvent
mixture to produce a solution containing 0.0002 per cent w/v of Thyroxine Sodium.
Reference solution. A 0.02 per cent w/v solution of levothyroxine sodium RS in a mixture of equal volumes of 0.1 M
sodium hydroxide and methanol. Dilute 1.0 ml of this solution to 100.0 ml with the solvent mixture. Further dilute
1.0 ml of this solution to 10.0 ml with the solvent mixture.
Calculate the content of C15H10I4NNaO4 in the tablet.
Assay.
Para 1 and 2, Change to:
Solvent mixture. A mixture of 600 volumes of water, 400 volumes of acetonitrile and 0.5 volume of ortho
phosphoric acid.
Test solution. Weigh and powder 20 or more tablets. Disperse a quantity of the powder containing about 1 mg of
Thyroxine Sodium, in 40 ml of the solvent mixture with the aid of ultrasound and dilute to 100.0 ml with the solvent
mixture.
Reference solution. A 0.01 per cent w/v solution of levothyroxine sodium RS in a mixture of equal volumes of 0.1 M
sodium hydroxide and methanol. Dilute 1.0 ml of this solution to 10.0 ml with the solvent mixture.
Travoprost. Page 2250
Specific optical rotation. Line 2
Change from: ethanol (95 per cent) at 20º.
to: ethanol at 365 nm.
Triamterene. Page 2256
Related substances. Change to:
Related substances. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 10 mg of the substance under examination in the mobile phase and dilute to 10.0 ml with the
mobile phase.
Reference solution (a). Dilute 1.0 ml of the test solution to 100.0 ml with the mobile phase. Further dilute 1.0 ml of
this solution to 10.0 ml with the mobile phase.
Reference solution (b). A 0.0005 per cent w/v solution of nitrosotriaminopyrimidine RS (triamterene impurity A RS)
in the mobile phase. Dilute 1.0 ml of this solution to 100.0 ml with the mobile phase.
Reference solution (c). Dissolve a suitable quantity of 2,7-diamino-6-phenylpteridin-4-ol RS (triamterene impurity
B RS) in 0.5 ml of the mobile phase with the aid of ultrasound. To this solution, add 0.5 ml of the test solution.
Chromatographic system
– a stainless steel column 25 cm x 4 mm, packed with octadecylsilane bonded to porous silica (5 µm),
– mobile phase: a mixture of 0.2 volume of butylamine, 20 volumes of acetonitrile, 20 volumes of methanol and
60 volumes of water, adjusted to pH 5.3 with acetic acid,
– flow rate: 1 ml per minute,
– spectrophotometer set at 320 nm and 355 nm,
– injection volume: 50 µl.
The relative retention time with reference to triamterene for triamterene impurity A is about 0.6, for triamterene
impurity B is about 0.8 and for triamterene impurity C is about 1.7.
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IPC/7035/IP-2010/AL-4
Inject reference solutions (b) and (c). The test is not valid unless the resolution between the peaks due to triamterene
impurity B and triamterene at 355 nm is not less than 1.5 in the chromatogram obtained with reference solution (c) if
necessary, increase the quantity of water in the mobile phase and signal-to- noise ratio for the principal peak in the
chromatogram obtained with reference solution (b) at 320 nm is not less than 10.
Calculate the contents of the impurities in the test solution using the correction factors, 1.8 for triamterene impurity
B and 1.5 for triamterene impurity C.
Inject reference solutions (a), (b) and the test solution. In the chromatogram obtained with the test solution, the area
of any peak corresponding to triamterene impurity A at 320 nm is not more than the area of the corresponding peak
in the chromatogram obtained with reference solution (b) (50 ppm). The area of any peak corresponding to
triamterene impurities B and C at 355 nm is not more than the area of the principal peak in the chromatogram
obtained with reference solution (a) (0.1 per cent). The area of any other secondary peak at 355 nm is not more than
the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 per cent). The sum of
areas of all the secondary peaks at 355 nm is not more than twice the area of the principal peak in the chromatogram
obtained with reference solution (a) (0.2 per cent). Ignore any peak at 355 nm with an area less than 0.5 times the
area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).
Triprolidine Hydrochloride. Page 2268
Assay.
Change to: Weigh accurately about 0.25 g, dissolve in a mixture of 50 ml of anhydrous glacial acetic acid, 0.5 ml of
acetic anhydride and add 15 ml of mercuric acetate solution. Titrate with 0.1 M perchloric acid, using crystal violet
solution as indicator. Carry out a blank titration.
1 ml of 0.1 M perchloric acid is equivalent to 0.01574 g of C19H22N2, HCl.
Valsartan.
Page 2286
Specific optical rotation. Line 1,
Change from: -60º to -67º
to: -64º to -69º
Purified Water. Page 2314
Bacterial endotoxins. Change from: Not more than 0.25 Endotoxin unit per ml.
to: Not more than 0.25 Endotoxin unit per ml, if intended for use in the
manufacture of dialysis solutions without a further appropriate procedure for
removal of bacterial endotoxins.
Zinc Sulphate Monohydrate. Page 2970
Assay.Change to:
Assay. Dissolve 0.160 g in 5 ml of dilute acetic acid into a 500-ml conical flask and add 200 ml of water. Add about
500 mg of xylenol orange and hexamethylenetetramine until the solution becomes violet-pink; add 2 g of
hexamethylenetetramine in excess. Titrate with 0.1 M disodium edetate until the violet-pink colour changes to
yellow.
1 ml of 0.1 M disodium edetate is equivalent to 0.01795 g of ZnSO4,H2O.
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