盐酸氟桂利嗪BP2013

BritishPharmacopoeiaVolumeI&IIMonographs:MedicinalandPharmaceuticalSubstances FlunarizineDihydrochloride GeneralNotices(Ph.Eur.monograph1722)C26H28Cl2F2N2    477.4    30484-77-6ActionanduseCalciumchannelblocker.PhEurDEFINITION1-[Bis(4-fluorophenyl)methyl]-4-[(2E)-3-phenylprop-2-enyl]piperazinedihydrochloride.Content99.0percentto101.5percent(driedsubstance).CHARACTERSAppearanceWhiteoralmostwhitepowder,hygroscopic.SolubilitySlightlysolubleinwater,sparinglysolubleinmethanol,slightlysolubleinalcoholandinmethylenechloride.mpAbout208 °C,withdecomposition.IDENTIFICATIONA.Infraredabsorptionspectrophotometry(2.2.24).Comparison   Ph.Eur.referencespectrumofflunarizinedihydrochloride.B.Dissolve25mgin2mLof methanolR andadd0.5mLof waterR.Thesolutiongivesreaction(a)ofchlorides(2.3.1).TESTSRelatedsubstancesLiquidchromatography(2.2.29). Preparethesolutionsimmediatelybeforeuseandprotectfromlight.Testsolution  Dissolve0.100gofthesubstancetobeexaminedin methanolR anddiluteto10.0mLwiththesamesolvent.Referencesolution(a)  Dissolve10mgof flunarizinedihydrochlorideforsystemsuitabilityCRS in methanolR anddiluteto1.0mLwiththesamesolvent.Referencesolution(b)  Dilute1.0mLofthetestsolutionto100.0mLwith methanolR.Dilute5.0mLofthissolutionto20.0mLwith methanolR.Column:— size:l =  0.10m,Ø = 4.6mm,— stationaryphase: base-deactivatedoctadecylsilylsilicagelforchromatographyR (3µm).Mobilephase:— mobilephaseA: solutioncontaining23.8g/Lof tetrabutylammoniumhydrogensulfateR and7g/Lof ammoniumacetateR,— mobilephaseB:acetonitrileR,Flowrate  1.5mL/min.Detection  Spectrophotometerat230nm.Injection  10µL.Systemsuitability  Referencesolution(a):— peak-to-valleyratio:minimum1.5,where Hp = heightabovethebaselineofthepeakduetoimpurityCand Hv = heightabovethebaselineofthelowestpointofthecurveseparatingthispeakfromthepeakduetoflunarizine,—thechromatogramobtainedisconcordantwiththechromatogramsuppliedwith flunarizinedihydrochlorideforsystemsuitabilityCRS.Limits:— correctionfactor: forthecalculationofcontent,multiplythepeakareaofimpurityAby1.5,— impuritiesA,D: foreachimpurity,notmorethan0.4timestheareaoftheprincipalpeakinthechromatogramobtainedwithreferencesolution(b)(0.1percent),— impurityB: notmorethantwicetheareaoftheprincipalpeakinthechromatogramobtainedwithreferencesolution(b)(0.5percent),— impurityC: notmorethantheareaoftheprincipalpeakinthechromatogramobtainedwithreferencesolution(b)(0.25percent),— anyotherimpurity: foreachimpurity,notmorethan0.4timestheareaoftheprincipalpeakinthechromatogramobtainedwithreferencesolution(b)(0.1percent),— total: notmorethan4timestheareaoftheprincipalpeakinthechromatogramobtainedwithreferencesolution(b)(1.0percent),— disregardlimit: 0.2timestheareaoftheprincipalpeakinthechromatogramobtainedwithreferencesolution(b)(0.05percent).Lossondrying(2.2.32)Maximum5.0percent,determinedon1.000gbydryinginanovenat105 °Cfor4h.Sulfatedash(2.4.14)Maximum0.1percent,determinedon1.0ginaplatinumcrucible.ASSAYDissolve0.200gin70mLof alcoholR.Carryoutapotentiometrictitration(2.2.20),using 0.1Msodiumhydroxide.Readthevolumeaddedatthesecondpointofinflexion.Carryoutablanktitration.1mLof 0.1Msodiumhydroxide isequivalentto23.87mgofC26H28Cl2F2N2.STORAGEInanairtightcontainer,protectedfromlight.IMPURITIESSpecifiedimpurities   A,B,C,D.A.1-[bis(4-fluorophenyl)methyl]piperazine,B.R1 = R2 = R3 = H,R4 = C6H5:1-[(RS)-(4-fluorophenyl)phenylmethyl]-4-[(2E)-3-phenylprop-2-enyl]piperazine,C.R1 = F,R2 = R3 = H,R4 = C6H5:1-[(RS)-(2-fluorophenyl)(4-fluorophenyl)methyl]-4-[(2E)-3-phenylprop-2-enyl]piperazine,D.R1 = R4 = H,R2 = F,R3 = C6H5:1-[bis(4-fluorophenyl)methyl]-4-[(2Z)-3-phenylprop-2-enyl]piperazine.PhEur