DRAFT PROPOSAL FOR AMENDMENTS IP2014
UPDATED ON: 17.04.2012
The IPC has received inputs from its stakeholders on IP 2010 which require upgradation/change. The draft
amendments (PROPOSED) are put on the website (www.ipc.gov.in) for comments of the users. It is expected that if
no comments are received within 21 days, please note- the draft amendments will be taken for finalization
General Chapters
2.2.9. Microbial Contamination in Non Sterile Products. Page 37
Preparation of the inoculum. Page 43
Microorganism used. Line 5
Change from: Shigella boydii to: Shigella boydii ATCC8700 or NCTC 12985
Fatty products. Line 11
Insert the following after “not more than 30 minutes”
Adjust the volume to 100 ml with the same medium.
4.3. Indicators and Indicator Test Papers
Bromocresol Green-Methyl Red Solution. 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.
2.4.26. Solubility
Famotidine. Page 156
Change to: Freely soluble in dimethylformamide and in glacial acetic acid; slightly soluble in methanol; very
slightly soluble in water; practically insoluble in acetone, in ethanol (95 per cent), in chloroform, in ether and in
ethyl acetate.
Monographs
Alprazolam Tablets. Page 787
Dissolution. Chromatographic system, line 2
Change from: octadecylsilane to: octylsilane
S-Amlodipine Besylate. Page 808
Structure and lines 1 to 4
Change to:
Cl
O
O H
H3CO
H3C
N
H
SO3H
O
O
C26H31ClN2O8S, 2.5H2O.
CH3
,
,
2
1
H2O
2
NH2
Mol. Wt. 612.1
1
DRAFT PROPOSAL FOR AMENDMENTS IP2014
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).
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 under 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 between amlodipine and 3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2chlorophenyl)-6-methylpyridine-3,5-dicarboxylate (amlodipine impurity D) is about 0.5.
Inject the reference solution and the test solution. In the chromatogram obtained with the test solution the area of
any peak obtained due to impurity D multiplied by 2 is not more than 1.5 times the area of the principal peak in the
chromatogram obtained with reference solution (b) (0.3 per cent) and sum of the area 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 due to benzene sulphonic acid (Relative retention time is about 0.14).
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.
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.
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-[(42
DRAFT PROPOSAL FOR AMENDMENTS IP2014
methylphenyl)sulfonyl]azithromycin (azithromycin impurity
(azithromycin impurity B) is about 1.31.
G) is about 1.26; for 3-deoxyazithromycin
Last para, insert at the end
;ignore the peaks eluting before impurity L and after impurity B.
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 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
Test B: Delete the requirement
Cefaclor Oral Suspension. Page 995
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.
3
DRAFT PROPOSAL FOR AMENDMENTS IP2014
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 peak due to cefuroxime axetil D3-isomers is not more than 1.5 times the area of the principal peaks in the
chromatogram obtained with reference solution (a) (1.5 per cent), the area of peak due to cefuroxime axetil Eisomers is not more than 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 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 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 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 under 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.
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
Change Uniformity of content and Assay 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. For tablets containing less than 250 µg, add 2 ml of water to one tablet in an amber-coloured flask and
disperse with the aid of ultrasound. Add 6 ml of dimethyl sulphoxide, mix, extract with 25 ml of hexane by shaking
4
DRAFT PROPOSAL FOR AMENDMENTS IP2014
for 30 minutes, centrifuge the hexane layer and use the clear supernatant liquid. For tablets containing more than
250 µg, prepare the solution in the same manner but using 4 ml of water, 12 ml of dimethyl sulphoxide and 100 ml
of hexane, and dilute to obtain a final concentration of 0.001 per cent w/v solution.
Assay. Determine by liquid chromatography (2.4.14).
NOTE- Carry out the following procedure as rapidly as possible in subdued light and protected from air.
Test solution. Weigh and powder 20 tablets. Weigh accurately a quantity of the powder containing about 250 µg of
Calciferol, disperse in 4 ml of water. Add 12 ml of dimethyl sulphoxide, mix, extract with 100 ml of hexane by
shaking for 30 minutes, centrifuge the hexane layer and use the clear supernatant liquid, and dilute to obtain a final
concentration of 0.001 per cent w/v solution.
Reference solution (a). A 0.001 per cent w/v solution of cholecalciferol RS or ergocalciferol RS, as appropriate.
Reference solution (b). Dissolve 50 mg of cholecalciferol RS or ergocalciferol RS as appropriate in 10 ml of toluene
without heating and dilute with the mobile phase to 100.0 ml. Dilute 5.0 ml of this solution to 50.0 ml with the
mobile phase. Reflux 5.0 ml of this solution, under nitrogen, using a water-bath, for 60 minutes to obtain a solution
of cholecalciferol, precholecalciferol and trans-cholecalciferol. Cool and dilute the refluxed solution to 50.0 ml with
the mobile phase.
Chromatographic system
– a stainless steel column 25 cm x 4.6 mm, packed with porous silica or ceramic microparticles (3 to 10 µm)
(Such as Nucleosil 50-S 5 µm),
– mobile phase: a mixture of 997 volumes of hexane and 3 volumes of 1-pentanol,
– flow rate: 2 ml per minute,
– spectrophotometer set at 254 nm,
– injection volume: 10 or 20 µl.
Inject a suitable volume of reference solution (b). Adjust the sensitivity so that the height of the peak due to
cholecalciferol is more than 50 per cent of the full-scale deflection. Record the chromatograms after five more
injections. The approximate relative retention times calculated with reference to cholecalciferol are 0.4 for
precholecalciferol and 0.5 for trans-cholecalciferol. The resolution between precholecalciferol and transcholecalciferol should be not less than 1.0; if necessary adjust the proportions of the constituents and flow rate of the
mobile phase to obtain the required resolution.
Inject reference solution (a). Adjust the sensitivity so that the height of the peak due to cholecalciferol or
ergocalciferol is more than 50 per cent of the full-scale deflection.
Inject reference solution (a) and the test solution.
Calculate the content of cholecalciferol, C27H44O, or ergocalciferol, C28H44O in the tablets.
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]-3,155
DRAFT PROPOSAL FOR AMENDMENTS IP2014
oxabicyclo[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.
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 2901
Assay. Test solution. Change to:
Test solution. Weigh and powder 20 tablets. Disperse a quantity of 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.
6
DRAFT PROPOSAL FOR AMENDMENTS IP2014
Reference solution (b). Dissolve 5 mg of diphenhydramine impurity A RS and 5 mg of diphenylmethanol 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.
Inject reference solution (b). The test is not valid unless the resolution between the peaks due to diphenhydramine
and diphenhydramine impurity A is not less than 2.0. The relative retention time with reference to diphenhydramine
for diphenhydramine impurity A (2-(diphenylmethoxy)-N-methylethanamine) is about 0.9, for diphenhydramine
impurity B (2-[(RS)-(4-methylphenyl)phenylmethoxy]-N,N- dimethylethanamine) is about 1.5, diphenhydramine
impurity C (2-[(RS)-(4-bromophenyl)phenylmethoxy]-N,N- dimethylethanamine) is about 1.8, for diphenhydramine
impurity D (benzhydrol) is about 2.6 and diphenhydramine impurity E (benzophenone) is about 5.1. The correction
factor for diphenhydramine impurity D is 0.7
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 the reference solution (a) (0.05 per cent).
Enoxaparin Injection. Page 1279
Anti-factor IIa activity. Lines 1 and 2
Change from: Not less than 20.0 and not more than 35.0 anti-factor IIa IU per mg. to: Not less than 2000 and not
more than 3500 anti-factor IIa IU per ml.
Anti-factor Xa to anti-factor IIa ratio. Line 2 and 4,
Change from: IU per mg to: IU per ml
Erythromycin. Page 1290
Assay. Line 4
Change from: water to: sterile phosphate buffer pH 8.0
Erythromycin Tablets. Page 1291
Assay. Para 2, line 2 and 3
Change from: 0.4 g of Erythromycin and triturate with 10 ml of sterile phosphate buffer pH 8.0 to: 0.25 g of
Erythromycin and triturate with 10 ml of methanol.
Fenofibrate Capsules. Page 2912
Assay. Chromatograhic system, line 5
Change from: 136 g to: 136 mg
7
DRAFT PROPOSAL FOR AMENDMENTS IP2014
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, fluconazole impurity B is
1.29 and fluconazole impurity C is 0.05.
Fumaric Acid. Page 1394
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.
Glimepiride Tablets. Page 1419
Related substances. After chromatograhic system, para 1,
Iinsert at the end.
The correction factor for glimepiride impurity B is 0.77.
Griseofulvin Tablets. Page 1428
8
DRAFT PROPOSAL FOR AMENDMENTS IP2014
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.
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
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.
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
9
DRAFT PROPOSAL FOR AMENDMENTS IP2014
sonicate for 60 minutes in cool water with occasional shaking. Make up the volume with the solvent mixture.
Centrifuge at 3500 rpm for 15 minutes. Dilute it with the solvent mixture to prepare 0.01per cent 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).
Lansoprazole.
Page 1568
Related substances. Reference solution (b)
Change to: Reference solution (b). A 0.0025 per cent w/v solution of lansoprazole RS in methanol. Dilute 1.0 ml of
this solution to 10.0 ml with the solvent mixture.
Lansoprazole Sustained-release Capsules. Page 1570
Dissolution. Lines 13 and 14.
Change from: D. Not more than 10 per cent of the stated amount of C16H14F3N3O2S. to: Complies with the
acceptance criteria given under acid stage.
Levodopa and Carbidopa Tablets. Page 1576
Assay. Reference solution, line 3
Change from: 2 ml to: 50 ml
Loperamide Tablets.
Page 1601
Dissolution. Line 4 and 5
Change from: Withdraw 10 ml of the medium from each vessel, mix and filter.
Test solution. The mixed filtrate from the dissolution medium.
to: Withdraw a suitable volume of the medium and filter.
Test solution. Use the filtrate.
Losartan Potassium and Amlodipine Tablets. Page 2927
Dissolution. Reference solution. line 2
Change from: 0.025 per cent to: 0.035 per cent
Meropenem Injection.
Page 1656
10
DRAFT PROPOSAL FOR AMENDMENTS IP2014
Insert before Bacterial endotoxins
Sodium carbonate. Weigh accurately a quantity 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.
Mometasone Furoate. Page 1700
Related substances. Reference solution (b, line 2
Change from: 25.0 ml to: 20.0 ml
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.
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
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 0.1 M hydrochloric acid and dilute to 100.0 ml with the same solvent and filter.
Calculate the content of C18H19N3O in the tablets.
Ondansetron Oral Solution.
Page 1818
Related substances: Change to:
11
DRAFT PROPOSAL FOR AMENDMENTS IP2014
Related substances. Determined by liquid chromatography (2.4.14), as described under 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 the
peak due 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 principle 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 principle 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 principle 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 the following before Category
By convention, for the purpose of labeling oxytocin preparations, 1 mg of oxytocin peptide (C 43H66O12S2) is
equivalent to 600IU 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. Change to:
Related substances. Determine by liquid chromatography (2.4.14).
NOTE – Prepare the solutions immediately before use.
Test solution. Dissolve a quantity of the substance under examination containing 0.25 g of potassium clavulanate in
5 ml of mobile phase A, dilute to 25.0 ml with mobile phase A and filter.
12
DRAFT PROPOSAL FOR AMENDMENTS IP2014
Reference solution (a). Dilute 1.0 ml of the test solution to 100.0 ml with mobile phase A.
Reference solution (b). Dissolve 10 mg of amoxycillin trihydrate RS in 1 ml of the test solution and dilute to 100.0
ml with mobile phase A.
Chromatographic system
– a stainless steel column 10 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm),
– column temperature. 40°,
– mobile phase: A. a 0.78 per cent w/v solution of sodium dihydrogen phosphate adjusted to pH 4.0 with dilute
phosphoric acid,
B. a mixture of equal volumes of mobile phase A and methanol,
– flow rate: 1 ml per minute,
– a linear gradient programme using the conditions given below,
– spectrophotometer set at 230 nm,
– injection volume: 20 µl.
Time
Mobile phase A
Mobile phase B
(in min.)
(per cent v/v)
(per cent v/v)
0→4
100
0
4 → 15
100 → 50
0 → 50
15 →18
50
50
18 → 24
50 →100
50 → 0
Inject reference solution (b). The resolution between the clavulanate (first peak) and amoxycillin (second peak) is
not less than 13.
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).
Pralidoxime Chloride. Page 1944
Identification. B, line 4
Change from: 332 nm to: 336 nm
Pralidoxime Chloride Injection. Page 1944
Identification. B, line 4
Change from: 332 nm to: 336 nm
Prednisolone Tablets. Page 1952
Dissolution. Line 9
Change from: prednisolone RS. to: prednisolone RS prepared by dissolving in methanol and diluted with the
dissolution medium.
Pregabalin Capsules. Page 1961
Related substances. Change to:
Related substances. Determine by liquid chromatography (2.4.14).
13
DRAFT PROPOSAL FOR AMENDMENTS IP2014
Solvent mixture. Dissolve 1.2 g of potassium dihydrogen phosphate in 1000 ml of water, adjust the pH to 6.9 with
dilute potassium hydroxide.
Test solution. Mix the content of 10 capsules. Weigh and disperse a quantity containing about 15 mg of Pregabalin,
in about 25 ml of the solvent mixture, sonicate for 30 minutes and dilute to 100.0 ml with the solvent mixture.
Reference solution. A 0.00015 per cent w/v solution of pregabalin RS in the solvent mixture.
Chromatographic system
– a stainless steel column 25 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm) (Such as
Inertsil ODS-3V),
– mobile phase
A: a mixture of 90 volumes of the solvent mixture and 10 volumes of acetonitrile,
B: acetonitrile,
– a linear gradient programme using the conditions given below,
– flow rate: 1 ml per minute,
– spectrophotometer set at 210 nm,
– injection volume: 20 µl.
Time
Mobile phase A
Mobile phase B
(in min.)
(per cent v/v)
(per cent v/v)
0
100
0
5
100
0
25
35
65
30
100
0
40
100
0
Inject the reference solution. The test is not valid unless the theoretical plates is not less than 3000, the tailing factor
is not more than 2.0 and the relative standard deviation of replicate injections is not more than 2.0 per cent.
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 the area of the principal peak in the chromatogram obtained with the reference
solution (1.0 per cent) and 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 the reference solution (2.5 per cent). Ignore any peak with an area
less than 0.05 times of the area of principal peak in the chromatogram obtained with the reference solution (0.05 per
cent).
Primaquine Tablets. Page 1964
Change the monograph to: Primaquine Tablets
Primaquine Phosphate Tablets
Primaquine Tablets contain not less than 90.0 per cent and not more than 110.0 per cent of the stated amount of
primaquine, C15H21N3O.
Usual strength. The equivalent of 2.5 mg of primaquine (13 mg of Primaquine Phosphate is approximately
equivalent to 7.5 mg of primaquine).
Identification
A.
Dissolve
a
quantity
of
the
powdered
tablets
containing
60 mg of primaquine in a mixture of 10 ml of water and 2 ml of 2 M sodium hydroxide and extract with two
quantities, each of 20 ml, of chloroform. Wash the chloroform extracts with water, dry over anhydrous sodium
sulphate, evaporate to dryness and dissolve the residue in 2 ml of chloroform. The residue complies with the
following test.
Determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained with
primaquine phosphate RS or with the reference spectrum of primaquine.
14
DRAFT PROPOSAL FOR AMENDMENTS IP2014
B. Extract a quantity of the powdered tablets containing 25 mg of primaquine with 10 ml of water and filter. To 2 ml
of the filtrate, add 3 ml of water and 1 ml of a 5 per cent w/v solution of ceric ammonium sulphate in 2 M nitric
acid; a deep violet colour is produced immediately.
Tests
Dissolution (2.5.2).
Apparatus No. 1,
Medium. 900 ml of 0.01 M hydrochloric acid,
Speed and time. 50 rpm and 60 minutes.
Withdraw a suitable volume of the medium and filter.
Determine by liquid chromatography (2.4.14).
Test solution. Dilute the filtrate, if necessary, with the dissolution medium.
Reference solution. A 0.0003 per cent w/v solution of primaquine phosphate RS in the dissolution medium.
Chromatographic system
– a stainless steel column 30 cm x 3.9 mm, packed with octadecylsilane bonded to porous silica (3 µm),
– column temperature. 30º,
– mobile phase: a mixture of 40 volumes of 1- pentane sulphonate sodium solution prepared by dissolving 961
mg of sodium-1- pentane sulphonate and 1 ml glacial acetic acid to 400 ml of water and 60 volumes of
methanol,
– flow rate. 1.2 ml per minute,
– spectrophotometer set at 254 nm,
– injection volume. 20 µl.
Inject the reference solution. The test is not valid unless the relative standard deviation for replicate injections is not
more than 3.0 per cent.
Inject the reference solution and the test solution.
D. Not less than 75 per cent of the stated amount of C15H21N3O.
Uniformity of content. (For tablets containing 10 mg or less) Comply with the test stated under tablets.
Determine by liquid chromatography (2.4.14), as described under Assay, using the following solution as the test
solution.
Test
solution.
Powder
one
tablet,
transfer
to
a
25-ml
volumetric
20 ml of the mobile phase and shake and dilute to volume with the mobile phase and filter.
flask,
add
Calculate the content of C15H21N3O in the tablet.
Other tests. Comply with the tests stated under Tablets.
Assay. Determine by liquid chromatography (2.4.14).
Test solution. Weigh and powder 20 tablets. Weigh accurately a quantity of the powder containing 10 mg of
primaquine, dissolve in 30 ml of the mobile phase and sonicate for 20 minutes. Make up the volume to 50.0 ml with
mobile phase.
15
DRAFT PROPOSAL FOR AMENDMENTS IP2014
Reference solution. A 0.02 per cent w/v solution of primaquine phosphate RS in the mobile phase.
Chromatographic system
– a stainless steel column 15 cm x 3.0 mm, packed with octadecylsilane bonded to porous silica (3 µm),
– column temperature. 30º,
– mobile phase: a mixture of 40 volumes of 1- pentane sulphonate sodium solution prepared by dissolving 960
mg of sodium-1- pentane sulphonate and 1 ml glacial acetic acid to 400 ml of water and 60 volumes of
methanol,
– flow rate. 0.6 ml per minute,
– spectrophotometer set at 264 nm,
– injection volume. 5 µl.
Inject the reference solution. The test is not valid unless the column efficiency in not less than 2000 theoretical
plates, 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 the reference solution and the test solution.
Calculate the content of C15H21N3O.
Storage. Store protected from moisture.
Labelling. The label states the strength in terms of the equivalent amount of primaquine.
Ramipril and Hydrochlorothiazide Tablets. Page 2041
Uniformity of content. Change to:
Uniformity of content. Comply with the test stated under Tablets.
Determine by liquid chromatography (2.4.14), as described under Assay.
Test solution. Disperse 1 intact tablet in water and dilute to 25.0 ml with the mobile phase. Dilute 3.0 ml of this
solution to 25.0 ml with the mobile phase and mix.
Assay. Change to:
Assay. Determine by liquid chromatography (2.4.14).
Test solution. Weigh and powder 20 tablets. Weigh accurately a quantity of powder containing about 25 mg of
Ramipril, disperse in water and dilute to 250.0 ml with the mobile phase, filter. Dilute 3.0 ml of this solution to 25.0
ml with the mobile phase and mix.
Reference solution (a). A 0.024 per cent w/v solution of ramipril RS in the mobile phase.
Reference solution (b). A 0.06 per cent w/v solution of hydrochlorothiazide RS in the mobile phase.
Reference solution (c). Dilute reference solution (a) and (b) with the mobile phase to obtain a solution having a
known concentration similar to the test solution.
Chromatographic system
– a stainless steel column 25 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm) (Such as
Thermo quest Hypersil),
– mobile phase: a mixture of 55 volumes of water, 45 volumes of acetonitrile and 0.1 volume of triethylamine,
adjusted to pH 3.0 with orthophosphoric acid,
– flow rate: 1 ml per minute,
16
DRAFT PROPOSAL FOR AMENDMENTS IP2014
– spectrophotometer set at 210 nm,
– injection volume: 20 µl.
Inject reference solution (c). The test is not valid unless the relative standard deviation for replicate injections for
each peak is not more than 2.0 per cent.
Inject reference solution (c) and the test solution.
Calculate the content of C23H32N2O5 and C7H8ClN3O4S2 in the tablet.
Related substances. Last para, last line
Insert at the end
Ignore the peak due to hydrochlorthiazide.
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.
Secnidazole. Page 2095
Related substances. After chromatographic system, para 1, line 2
Change from: 2-methyl-4-nitroimidazole to: 2-methyl-5-nitroimidazole
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.
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
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
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.
17
DRAFT PROPOSAL FOR AMENDMENTS IP2014
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 dilute to 1000 ml with water.
Thyroxine Tablets. Page 2222
Usual strength. Change to:
Usual strengths. 50 µg; 100 µg
Uniformity of content. Change to:
Uniformity of content. Complies with the test stated under Tablets 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.
Follow the procedure described under Assay.
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.
18
DRAFT PROPOSAL FOR AMENDMENTS IP2014
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 the contents of a vial of triamterene impurity B RS (2,7-diamino-6-phenylpteridin4-ol 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.
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)
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 the peak due 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 the peak due to triamterene impurity 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
19
DRAFT PROPOSAL FOR AMENDMENTS IP2014
Assay.
Change to: Dissolve 0.160 g in 5 ml of dilute acetic acid into a 500-ml conical flask and dilute to 200 ml with 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.
Blood and Blood-related Products
Human Albumin. Page 2568
Abnormal toxicity. Line 2
Change from: using Method B to: for antisera and vaccines.
Veterinary Preparations. Page 2621
General Requirements
Insert after Para 1
The active pharmaceutical ingredients (drug substances), excipients (pharmaceutical aids), pharmaceutical
preparations (dosage forms) and other articles described in the monographs are intended for human and veterinary
use (unless explicitly restricted to one of these users).
20