Determination of Fulvestrant in Rat Plasma by LC–MS–MS教程.pdfVIP

Chromatographia (2011) 74:227–234 DOI 10.1007/s10337-011-2071-x ORIGINAL Determination of Fulvestrant in Rat Plasma by LC–MS–MS: Application to a Pharmacokinetic Study Zhongyang Liu • Guangzhi Gu • Huimin Xia • Qiang Liu • Zhiqing Pang • Xinguo Jiang • Jun Chen Received: 5 October 2010 / Revised: 9 May 2011 / Accepted: 13 May 2011 / Published online: 25 June 2011 Springer-Verlag 2011 Abstract A reversed-phase liquid chromatography cou- Introduction pled to tandem mass spectrometry (LC–MS–MS) method was developed and validated for the determination of ful- Fulvestrant, (7a,17b)-7-[9-[(4,4,5,5,5-pentafluoropentyl)sulfi- vestrant in rat plasma. Sample preparation involved a nyl]nonyl]estra-1,3,5(10)-triene-3,17-diol, is a novel endo- liquid-liquid extraction using 1.0 mL of n-hexane–isopro- crine therapy for breast cancer with a unique structure and panol (90:10, v/v) to extract the analyte from 0.1 mL of rat mode of action. It binds competitively to the estrogen receptor plasma. The analytes were separated on a phenyl-based (ER) with higher affinity than tamoxifen and downregulates column using the mobile phase consisting of methanol/ cellular levels of the ER protein, resulting in complete abro- water containing 5 mM ammonium acetate at the flow rate gation of estrogen-sensitive gene transcription [1–3]. Because of 0.3 mL min-1. The analytes were monitored by tandem it has a different mode of action than other hormonal agents, mass spectrometry under electrospray negative ionization fulvestrant is effective in the treatment of tamoxifen-resistant mode. Linear calibration curves were generated over the disease and, unlike tamoxifen, has no known estrogen agonist fulvestrant concentration ranges of 0.05–10.0 ng mL-1 in effects. Fulvestrant is currently lice