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1、Chromatographia(2011)74:227234DOI10.1007/s10337-011-2071-xORIGINALDeterminationofFulvestrantinRatPlasmabyLC–MS–MS:ApplicationtoaPharmacokineticStudyZhongyangLiu•GuangzhiGu•HuiminXia•QiangLiu•ZhiqingPang•XinguoJiang•JunChenReceived:5October2010/Revised:9May2011/Accepted:
2、13May2011/Publishedonline:25June2011ÓSpringer-Verlag2011AbstractAreversed-phaseliquidchromatographycou-Introductionpledtotandemmassspectrometry(LCMSMS)methodwasdevelopedandvalidatedforthedeterminationofful-Fulvestrant,(7a,17b)-7-[9-[(4,4,5,5,5-pentafluoropentyl)sulfi-vest
3、rantinratplasma.Samplepreparationinvolvedanyl]nonyl]estra-1,3,5(10)-triene-3,17-diol,isanovelendo-liquid-liquidextractionusing1.0mLofn-hexaneisopro-crinetherapyforbreastcancerwithauniquestructureandpanol(90:10,v/v)toextracttheanalytefrom0.1mLofratmodeofaction.Itbindscom
4、petitivelytotheestrogenreceptorplasma.Theanalyteswereseparatedonaphenyl-based(ER)withhigheraffinitythantamoxifenanddownregulatescolumnusingthemobilephaseconsistingofmethanol/cellularlevelsoftheERprotein,resultingincompleteabro-watercontaining5mMammoniumacetateattheflowrat
5、egationofestrogen-sensitivegenetranscription[13].Because-1of0.3mLmin.Theanalytesweremonitoredbytandemithasadifferentmodeofactionthanotherhormonalagents,massspectrometryunderelectrospraynegativeionizationfulvestrantiseffectiveinthetreatmentoftamoxifen-resistantmode.Linea
6、rcalibrationcurvesweregeneratedoverthediseaseand,unliketamoxifen,hasnoknownestrogenagonist-1fulvestrantconcentrationrangesof0.0510.0ngmLineffects.Fulvestrantiscurrentlylicensedforuseinpostmen-ratplasma.Theaccuracyandwithin-andbetween-dayopausalwomenwithhormonereceptor-p
7、ositiveadvancedprecisionswerewithinthegenerallyacceptedcriteriaforbreastcancerthathasprogressedonpriorendocrinetherapy.bioanalyticalmethods(15%).Thisdevelopedandvali-Inordertoachieveeffectiveinhibitionofestrogen-controlleddatedassaymethodwassuccessfullyemployedtocharac
8、-proliferation,downregulationoftheERmustbesustainedterizetheplasmaconcentration-timeprofileoffulvestrantovertim