首页|Validated LC-MS/MS method for simultaneous determination of SIM and its acid form in human plasma and cell lysate: Pharmacokinetic application

Validated LC-MS/MS method for simultaneous determination of SIM and its acid form in human plasma and cell lysate: Pharmacokinetic application

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Simvastatin (SIM) is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor widely used in hyperlipidemia therapy. SIM has recently been studied for its anticancer activity at doses higher than those used for the hyperlipidemia therapy. This prompted us to study the pharmacokinetics of high-dose SIM in cancer patients. For this purpose, an LC-MS/MS method was developed to measure SIM and its acid form (SIMA) in plasma and peripheral blood mononuclear cells (PBMCs) obtained from patients. Chromatographic analyte separation was carried out on a reverse-phase column using 75:25 (% v/v) acetonitrile:ammonium acetate (0.1 M, pH 5.0) mobile phase. Detection was performed on a triple quadrupole mass spectrometer, equipped with a turbo ion spray source and operated in positive ionization mode. The assay was linear over a range 2.5-500 ng/mL for SIM and 5-500 ng/mL for SIMA in plasma and 2.5-250 ng/mL for SIM and 5-250 ng/mL for SIMA in cell lysate. Recovery was 〉 58% for SIM and 〉 75% for SIMA in both plasma and cell lysate. SIM and SIMA were stable in plasma, cell lysate and the reconstitution solution. This method was successfully applied for the determination of SIM and SIMA in plasma and PBMCs samples collected in the pharmacokinetic study of high-dose SIM in cancer patients.

SimvastatinLC-MS/MSHuman plasmaCell lysatePharmacokineticHigh-dose

Tamer A. Ahmed、Jamie Horn、John Hayslip、Markos Leggas

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Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Avenue, Lexington, Kentucky 40536-0596, USA

Markey Cancer Center, University of Kentucky, 800 Rose Street, Lexington, Kentucky 40536-0293, USA

Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Avenue, Lexington, Kentucky 40536-0596, USA Markey Cancer Center, University of Kentucky, 800 Rose Street, Lexington, Kentucky 40536-0293, USA

细胞裂解液 药代动力学 SIM卡 LC-MS 同时测定 人血浆 MS法 应用

2012

西安医科大学学报(英文版)
西安交通大学

西安医科大学学报(英文版)

影响因子：0.07
ISSN：1671-8267
年,卷(期)：2012.2(6)
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