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BritishPharmacopoeiaVolumeI&II

Industrial Monographs:MedicinalandPharmaceuticalSubstances

Cyber Naproxen

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(PhEurmonograph0731)

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C14 H14 O3 230.322204531
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DEFINITION

(2S)2(6Methoxynaphthalen2yl)propanoicacid.

Content

99.0percentto101.0percent(driedsubstance).

CHARACTERS

Appearance

Whiteoralmostwhite,crystallinepowder.

Solubility

Practicallyinsolubleinwater,solubleinethanol(96percent)andinmethanol.

IDENTIFICATION

FirstidentificationA,D.

SecondidentificationA,B,C.

A.Specificopticalrotation(2.2.7):+59to+62(driedsubstance).

Dissolve0.50ginethanol(96percent)Randdiluteto25.0mlwiththesamesolvent.

B.Meltingpoint(2.2.14):154Cto158C.

C.Dissolve40.0mginmethanolRanddiluteto100.0mlwiththesamesolvent.Dilute10.0mlof
thesolutionto100.0mlwithmethanolR.Examinedbetween230nmand350nm(2.2.25),the
solutionshows4absorptionmaxima,at262nm,271nm,316nmand331nm.Thespecific
absorbancesattheabsorptionmaximaare216to238,219to241,61to69and79to87,
respectively.
 D.Infraredabsorptionspectrophotometry(2.2.24).

ComparisonnaproxenCRS.

TESTS

Appearanceofsolution

Thesolutionisclear(2.2.1)andnotmoreintenselycolouredthanreferencesolutionBY7 (2.2.2,
MethodII).

Dissolve1.25ginmethanolRanddiluteto25mlwiththesamesolvent.

Enantiomericpurity

Liquidchromatography(2.2.29).Protectthesolutionsfromlight.

TestsolutionDissolve25.0mgofthesubstancetobeexaminedintetrahydrofuranRanddiluteto
50.0mlwiththesamesolvent.Dilute2.0mlofthissolutionto20.0mlwiththemobilephase.

Referencesolution(a)Dilute2.5mlofthetestsolutionto100.0mlwiththemobilephase.

Referencesolution(b)Dissolve5mgofracemicnaproxenCRSin10mloftetrahydrofuranRand
diluteto100mlwiththemobilephase.

Column:

size:l=0.25m,=4.6mm,

stationaryphase:silicagelacceptor/donorforchiralseparationsR(5m)(S,S),

temperature:25C.

MobilephaseglacialaceticacidR,acetonitrileR,2propanolR,hexaneR(5:50:100:845V/V/V/V).

Flowrate2ml/min.

DetectionSpectrophotometerat263nm.

Injection20l.

Runtime1.5timestheretentiontimeofnaproxen(retentiontime=about5min).

SystemsuitabilityReferencesolution(b):

resolution:minimum3betweenthepeaksduetoimpurityGandnaproxen.

Limit:

impurityG:notmorethantheareaoftheprincipalpeakinthechromatogramobtainedwith
referencesolution(a)(2.5percent).

Relatedsubstances

Liquidchromatography(2.2.29).Protectthesolutionsfromlight.

TestsolutionDissolve12mgofthesubstancetobeexaminedinthemobilephaseanddiluteto20
mlwiththemobilephase.

Referencesolution(a)Dilute1.0mlofthetestsolutionto50.0mlwiththemobilephase.Dilute1.0
mlofthissolutionto20.0mlwiththemobilephase.

Referencesolution(b)Dissolve6mgofbromomethoxynaphthaleneR(impurityN),6mgof1(6
methoxynaphthalen2yl)ethanoneR(impurityL)and6mgof(1RS)1(6methoxynaphthalen2
yl)ethanolR(impurityK)inacetonitrileRanddiluteto10mlwiththesamesolvent.To1mlofthis
solutionadd1mlofthetestsolutionanddiluteto50mlwiththemobilephase.Dilute1mlofthis
solutionto20mlwiththemobilephase.

Column:

size:l=0.10m,=4.0mm,

stationaryphase:octadecylsilylsilicagelforchromatographyR(3m),

temperature:50C.

MobilephaseMix42volumesofacetonitrileRand58volumesofa1.36g/lsolutionofpotassium
dihydrogenphosphateRpreviouslyadjustedtopH2.0withphosphoricacidR.
Flowrate1.5ml/min.

DetectionSpectrophotometerat230nm.

Injection20l.

Runtime1.5timestheretentiontimeofimpurityN.

RelativeretentionWithreferencetonaproxen(retentiontime=about2.5min):
impurityA=about0.5impurityH=about0.7impurityI=about0.75impurityK=about0.9
impurityL=about1.4impurityC=about1.5impurityE=about2.8impurityF=about4.4
impurityN=about5.3impurityJ=about6.1.

SystemsuitabilityReferencesolution(b):

resolution:minimum2.2betweenthepeaksduetoimpurityKandnaproxen.

Limits:

correctionfactor:forthecalculationofcontent,multiplythepeakareaofimpurityLby3.3

impuritiesA,C,E,F,H,I,J,L:foreachimpurity,notmorethantheareaoftheprincipalpeakin
thechromatogramobtainedwithreferencesolution(a)(0.1percent)

anyotherimpurity:foreachimpurity,notmorethantheareaoftheprincipalpeakinthe
chromatogramobtainedwithreferencesolution(a)(0.1percent)

total:notmorethan3timestheareaoftheprincipalpeakinthechromatogramobtainedwith
referencesolution(a)(0.3percent)

disregardlimit:0.5timestheareaoftheprincipalpeakinthechromatogramobtainedwith
referencesolution(a)(0.05percent).

Heavymetals(2.4.8)

Maximum20ppm.

1.0gcomplieswithlimittestC.Preparethereferencesolutionusing2mlofleadstandardsolution
(10ppmPb)R.

Lossondrying(2.2.32)

Maximum0.5percent,determinedon1.000gbydryinginanovenat100105Cfor3h.

Sulphatedash(2.4.14)

Maximum0.1percent,determinedon1.0g.

ASSAY

Dissolve0.200ginamixtureof25mlofwaterRand75mlofmethanolR.Titratewith0.1Msodium
hydroxide,using1mlofphenolphthaleinsolutionRasindicator.

1mlof0.1Msodiumhydroxideisequivalentto23.03mgofC14 H14 O3 .

STORAGE

Protectedfromlight.

IMPURITIES

SpecifiedimpuritiesA,C,E,F,G,H,I,J,L.

OtherdetectableimpuritiesB,D,K,M,N.

A.R1=R2=R3=H:(2S)2(6hydroxynaphthalen2yl)propanoicacid,

B.R1=H,R2=Cl,R3=CH3 :(2S)2(5chloro6methoxynaphthalen2yl)propanoicacid,
 C.R1=H,R2=Br,R3=CH3 :(2S)2(5bromo6methoxynaphthalen2yl)propanoicacid,

D.R1=H,R2=I,R3=CH3 :(2S)2(5iodo6methoxynaphthalen2yl)propanoicacid,

E.R1=R3=CH3 ,R2=H:methyl(2S)2(6methoxynaphthalen2yl)propanoate,

F.R1=C2 H5 ,R2=H,R3=CH3 :ethyl(2S)2(6methoxynaphthalen2yl)propanoate,

G.(2R)2(6methoxynaphthalen2yl)propanoicacid((R)enantiomer),

H.R=OH:6methoxynaphthalen2ol,

I.R=CH2 CO2 H:(6methoxynaphthalen2yl)aceticacid,

J.R=C2 H5 :2ethyl6methoxynaphthalene,

K.R=CHOHCH3 :(1RS)1(6methoxynaphthalen2yl)ethanol,

L.R=COCH3 :1(6methoxynaphthalen2yl)ethanone,

M.R=H:2methoxynaphthalene(nerolin),

N.R=Br:2bromo6methoxynaphthalene.

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