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Tel/Fax076086655310E-mailljhua123@126．com528467。WatersXterraMSC184.6mm×250mm5μm0.01mol·L－1pH3.2AB1.0mL·min－1265nm40℃。A、210.02～8.08、0.02～8.260.02～8.29mg·mL－1r≥0.99991.0、1.4、2.1ng、、n=9100.2%～102.9%RSDn=90.02%～0.66%。、、。Adoi10.11669/cpj.2013.08.018R917A1001－2494201308－0644－05DeterminationofRelatedSubstancesinLapatinibDitosylateTabletsbyHPLCLIUJun-huaLIANGXing-huiWANGBin-rongZhuhaiUnitedLaboratoriesCo.Ltd.Zhongshan528467ChinaABSTRACTOBJECTIVEToestablishadeterminationmethodoftherelatedsubstancesoflapatinibditosylatetabletsbyHPLC.METHODSWatersXterraMSC18column4.6mm×250mm5μmwasselected0.01mol·L－1sodiumdihydrogenphosphatesolutionpHadjustedto3.2withphosphoricacidwasmobilephaseAacetonitrilewasmobilephaseBandgradientelutionwasusedataflowrateof1.0mL·min－1.Thedetectionwavelengthwassetat265nmandthecolumntemperaturewas40℃.RE-SULTSLapatinibImpurityALAPA-2andLAPA-1hadgoodlinearityintherangeof0.02－8.080.02－8.26and0.02－8.29mg·mL－1respectivelyr≥0.9999.ThelimitsofquantitationLOQwere1.01.4and2.1ngrespectively.Theaveragerecoveryn=9wasintherangeof100.2%－102.9%andRSDsn=9wereintherangeof0.02%－0.66%.CONCLUSIONThemethodissimpleaccurateandspecificandcanquantitativelydeterminetherelatedsub-stancesoflapatinibditosylatetablets.KEYWORDSHPLClapatinibditosylatetabletrelatedsubstancelapatinibimpurityA2EGFRErbB12HER2ErbB2-3FOXO3A1。。、、。1LC－20ADGU－20A3LC－20ATSIL－20ACCTO－20ACSPD－M20ACBM－20AXS105DUSevenEasypH-。11110197.2%61.0%HPLCAImpurityAF154IMPC380R0992LAPA-2F154IMPB380R0971LAPA-120106300003201104180011FormosaLaboratoriesInc。250mgY55111208、20116401、20116402、20116403TykerbTM·446·ChinPharmJ2013AprilVol.48No.820134488250mgR520553。22.11WatersXterraMSC184.6mm×250mm5μm2HypersilC184.6mm×250mm5μm。10.01mol·L－1pH3.2AB1.0mL·min－11265nm。40℃10μL。2.2①0.1%-40∶60V/V10mg20mL0.4428mg·mL－1。②6mg10mL。③1mL100mL。④19.85mg10mL1.211mg·mL－1。⑤A、2、1A、2、199.29、100.1、99.52μg·mL－1。⑥1mL50mLA、1Tab.1HPLCDeterminationoflapatinibditosylatetabletsre-latedsubstanceslineargradientelutionprogramt/minMobilephaseA/%MobilephaseB/%070305653510653525208035208035.0170304570302、11.986、2.002、1.990μg·mL－1。1。2.32.3.1“2.2”、、、“2.10”100%10μL“2.1”2。11。2.3.2、1mol·L－1、1mol·L－1、、、4500±500lx10d。3。、1A、1、2Fig.1StructuredfigureoflapatinibimpurityALAPA-1andLAPA-2·546·20134488ChinPharmJ2013AprilVol.48No.82A－B－C－1－2－3－A4－25－6－1Fig.2Chromatogramofseparationtestofmixedknownimpuri-tiesinlapatinibditosylatetabletsA－blanksolutionB－mixedknownimpuritiesstandardsolutionC－solutionoftabletssolutionandmixedknownimpuritiessolution1－toluenesulfonicacid2－lapatinib3－lapatinibimpurityA4－LAPA-25－unknownimpurity6－LA-PA-10.3%。、、、。。、1.000。、、、。。2.4Y5511120834.8、6、7.2mg3A－B－C－D－E－F－G－H－I－1－2－3－4－5－6－Fig.3Chromatogramsofrelatedsubstancesoflapatinibditosy-latetabletsanditsrawmaterialA－blanksolutionB－rawmaterialsolutionC－tabletsolutionD－tabletsafteraciddestructionwaterbathE－tabletsalkalidestructionwaterbathF－tab-letsoxygendestructionG－tabletshotdestructionwaterbathH－tabletslightradiationdestructionI－auxiliarymaterialsdestruction1－notdestroyed2－hotdestruction3－lightdestruction4－aciddestruction5－oxygendestruction6－al-kalidestruction10mL“2.2”“2.2”10μL“2.1”。1.000。0.6mg·mL－1。2.5Y55111208·646·ChinPharmJ2013AprilVol.48No.8201344886mg“2.2”6。10μL。610.06%n=6。2.6Y551112086mg“2.2”25℃8h0、1、2、4、6、8h10μL。25℃8h±1.0%。2.7“2.2”200%、150%、100%、80%、20%、10%、0.02%1211、908.1、605.4、484.3、121.1、60.54、0.1211μg·mL－110μL。μg·mL－1Y=29618.4ρ－64985r=0.9999。2.8A、2、1“2.2”0.2%400%、200%、100%、80%、50%、10%、1%μg·mL－1。A、2、1Y=29718.1ρ－227.9r=1.0000、Y=19131.7ρ－621.3r=0.9999、Y=12710.4X+12.7r=1.0000。2.9“2.8”“2.2”。10∶13∶1A、2、11.0、1.4、2.1ng0.2、0.4、0.3ng。2.10A、21“2.2”1mLA、2120μg。Y5511120896mg910mL330.8、1、1.2mL“2.2”“2.2”1mLA、212μg。“2.1”2。2.11“2.1”ApH3.1、3.2、3.3C18pH3。pHA。2.12Y55111208、20116401、20116402、20116403R520553“2.1～2.2”4。2.n=9珋x±sTab.2Averagerecoveryofknownimpuritiesinlapatinibdito-sylatetablets.n=9珋x±sComponentsmadded/μgmmeanfound/μgRecovery/%Lapatinib16.4816.77±0.09101.8±0.5impurityA20.6020.76±0.05100.8±0.324.7225.00±0.07101.1±0.3LAPA-217.7118.23±0.12102.9±0.722.1422.25±0.13100.5±0.626.5726.64±0.18100.3±0.7LAPA-116.4516.70±0.06101.5±0.420.5720.61±0.05100.2±0.324.6824.98±0.02101.2±0.1·746·20134488ChinPharmJ2013AprilVol.48No.8A、210.10%《》23【DOSAGEANDADMINISTRATION】1250mg0.05%0.2%0.2%。0.2%。33.11、2A。265nmA、2、11.0、1.4、2.1ng。3.20.10%。《》0.2%0.2%1.0%。4、、。3ApHTab.3RobustnesstestofcolumnandmobilephaseApHvalueColumnMobilephaseApHvalueSingleimpuritytotalimpuritiescontent/%MainpeakpurityWatersXterraMSC183.20.060.061.0000DalianEliteHypersilC183.10.050.051.00003.20.060.061.00003.30.060.061.00004Tab.4DeterminationresultsofrelatedsubstancesoflapatinibditosylatetabletsImpurityLotNo.Numberofimpuritieswithcontentofmorethan0.05%Unknownimpurityt/minContent/%Singleimpurity/%Totalimpurities/%Y55111208129.140.050.050.0520116401129.260.060.060.0620116402129.2250.060.060.0620116403129.2260.060.060.06R520553129.2330.060.060.06REFERENCES1ZHANQ．LapatinibinbreastcancertreatmentJ．JIntOncol2007348596-599．2SFDACDE．TechnicalguidelinesforchemicaldrugimpuritiesED/OL．SFDACDE20072012－8－26．http//．cde．org．cn/atta