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UpdatedPh.Eur.9.0,effective01/01/2017

Nifedipine

GeneralNotices

(Ph.Eur.monograph0627)

C17H18N2O6346.321829254

Actionanduse

Calciumchannelblocker.

Preparations

NifedipineCapsules

ProlongedreleaseNifedipineCapsules

ProlongedreleaseNifedipineTablets

PhEur

DEFINITION

Dimethyl2,6dimethyl4(2nitrophenyl)1,4dihydropyridine3,5dicarboxylate.

Content

98.0percentto102.0percent(driedsubstance).

CHARACTERS

Appearance

Yellow,crystallinepowder.

Solubility

Practicallyinsolubleinwater,freelysolubleinacetone,sparinglysolubleinethanol.

Whenexposedtodaylightandtoartificiallightofcertainwavelengths,itreadilyconvertstoanitrosophenylpyridinederivative.Exposuretoultraviolet
lightleadstotheformationofanitrophenylpyridinederivative.

Preparesolutionsimmediatelybeforeuseinthedarkorunderlongwavelengthlight(>420nm)andprotectthemfromlight.

IDENTIFICATION

Firstidentification:B

Secondidentification:A,C,D

A.Meltingpoint(2.2.14):171Cto175C.
B.Infraredabsorptionspectrophotometry(2.2.24).

Comparison nifedipineCRS.
C.Thinlayerchromatography(2.2.27).

Testsolution Dissolve10mgofthesubstancetobeexaminedinmethanolRanddiluteto10mLwiththesamesolvent.

Referencesolution Dissolve10mgofnifedipineCRSinmethanolRanddiluteto10mLwiththesamesolvent.

Plate TLCsilicagelF 254plateR.

Mobilephase ethylacetateR,cyclohexaneR(40:60V/V).

Application 5L.

Development Over3/4oftheplate.

Drying Inair.

Detection Examineinultravioletlightat254nm.

Results Theprincipalspotinthechromatogramobtainedwiththetestsolutionissimilarinposition,appearanceat254nmandsizetotheprincipal
spotinthechromatogramobtainedwiththereferencesolution.

D.To25mginatesttube,add10mLofamixtureof1.5volumesofhydrochloricacidR,3.5volumesofwaterRand5volumesofalcoholRand
dissolvewithgentleheating.Add0.5gofzincRingranulesandallowtostandfor5minwithoccasionalswirling.Filterintoasecondtesttube,add
5mLofa10g/LsolutionofsodiumnitriteRtothefiltrateandallowtostandfor2min.Add2mLofa50g/LsolutionofammoniumsulfamateR,shake
vigorouslywithcareandadd2mLofa5g/LsolutionofnaphthylethylenediaminedihydrochlorideR.Anintenseredcolourdevelopswhichpersistsfor
notlessthan5min.

TESTS

ImpurityDandotherbasicimpurities

Transfer4gtoa250mLconicalflaskanddissolvein160mLofglacialaceticacidRusinganultrasonicbath.Titratewith0.1Mperchloricacidusing
0.25mLofnaphtholbenzeinsolutionRasindicatoruntilthecolourchangesfrombrownishyellowtogreen.Notmorethan0.48mLof0.1Mperchloric
acidisrequired(0.14percent).

Relatedsubstances

Liquidchromatography(2.2.29).

Testsolution Dissolve0.200gofthesubstancetobeexaminedin20mLofmethanolRanddiluteto50.0mLwiththemobilephase.

Referencesolution(a) Dissolve10mgofnifedipineimpurityACRSinmethanolRanddiluteto25.0mLwiththesamesolvent.

Referencesolution(b) Dissolve10mgofnifedipineimpurityBCRSinmethanolRanddiluteto25.0mLwiththesamesolvent.

Referencesolution(c) Mix1.0mLofreferencesolution(a),1.0mLofreferencesolution(b)and0.1mLofthetestsolutionanddiluteto20.0mLwith
themobilephase.Dilute2.0mLofthissolutionto10.0mLwiththemobilephase.

Column:
size:l=0.15m,=4.6mm,

stationaryphase:octadecylsilylsilicagelforchromatographyR(5m).

Mobilephase acetonitrileR,methanolR,waterR(9:36:55V/V/V).

Flowrate 1.0mL/min.

Detection Spectrophotometerat235nm.

Injection 20Linjectthetestsolutionandreferencesolution(c).

Runtime Twicetheretentiontimeofnifedipine.

Elutionorder ImpurityA,impurityB,nifedipine.

Retentiontime Nifedipine=about15.5min.

Systemsuitability:referencesolution(c):
resolution:minimum1.5betweenthepeaksduetoimpurityAandimpurityBandminimum1.5betweenthepeaksduetoimpurityBand
nifedipine.

Limits:
 impurityA:notmorethantheareaofthecorrespondingpeakinthechromatogramobtainedwithreferencesolution(c)(0.1percent),

impurityB:notmorethantheareaofthecorrespondingpeakinthechromatogramobtainedwithreferencesolution(c)(0.1percent),

anyotherimpurity:notmorethantheareaofthepeakduetonifedipineinthechromatogramobtainedwithreferencesolution(c)(0.1percent),

total:notmorethan0.3percent,

disregardlimit:0.1timestheareaofthepeakduetonifedipineinthechromatogramobtainedwithreferencesolution(c)(0.01percent).

Lossondrying(2.2.32)

Maximum0.5percent,determinedon1.000gbydryinginanovenat105Cfor2h.

Sulfatedash(2.4.14)

Maximum0.1percent,determinedon1.0g.

ASSAY

Dissolve0.1300ginamixtureof25mLof2methyl2propanolRand25mLofperchloricacidsolutionR.Titratewith0.1Mceriumsulfateusing
0.1mLofferroinRasindicator,untilthepinkcolourdisappears.Titrateslowlytowardstheendofthetitration.Carryoutablanktitration.

1mLof0.1Mceriumsulfateisequivalentto17.32mgofC17H18N2O6.

STORAGE

Protectedfromlight.

IMPURITIES

Specifiedimpurities:A,B,C,D.

A.dimethyl2,6dimethyl4(2nitrophenyl)pyridine3,5dicarboxylate(nitrophenylpyridineanalogue),

B.dimethyl2,6dimethyl4(2nitrosophenyl)pyridine3,5dicarboxylate(nitrosophenylpyridineanalogue),

C.methyl2(2nitrobenzylidene)3oxobutanoate,
D.methyl3aminobut2enoate.
PhEur

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