Development of a sensitive and selective LC-MS/MS method for simultaneous determination of gemcitabine and 2,2-difluoro-2-deoxyuridine in human plasma

被引:48
作者
Bowen, Chester [1 ]
Wang, Sherry [1 ]
Licea-Perez, Hermes [1 ]
机构
[1] GlaxoSmithKline, Worldwide Bioanal & Syst Management, Preclin Drug Metab & Pharmacokinet, King Of Prussia, PA 19406 USA
来源
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2009年 / 877卷 / 22期
关键词
Gemcitabine; 2,2-Difluoro-2-deoxyuridine; Derivatization; Dansyl chloride; Mass spectrometry; UPLC; PERFORMANCE LIQUID-CHROMATOGRAPHY; ANTICANCER AGENT GEMCITABINE; CELL LUNG-CANCER; METABOLITE; PHARMACOLOGY; TISSUE; DFDU;
D O I
10.1016/j.jchromb.2009.06.002
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A sensitive, selective, and quantitative method for the simultaneous determination of gemcitabine and 2,2-difluoro-2-deoxyuridine (dFdU) has been developed and validated in human plasma in the presence of tetrahydrouridine, a cytidine deaminase inhibitor. The method employs derivatization of gemcitabine and dFdU with dansyl chloride to improve the chromatographic retention and separation. The derivatization was performed in plasma without prior sample clean-up, followed by extraction of the dansyl-derivatives using methyl tertiary-butyl ether (MTBE). Ultra performance liquid chromatography (UPLC) technology on a BEH C18 stationary phase column with 1.7 mu m particle size was used for chromatographic separation coupled to tandem mass spectrometry. The method was validated over the concentration ranges of 20-5000 and 100-25,000 ng/mL for gemcitabine and dFdU, respectively. The results from assay validation show that the method is rugged, precise, accurate. and well-suited to support pharmacokinetic studies. In addition, the relatively small sample volume (50 mu L) and a run time of 1.5 min facilitate automation and allow for high-throughput analysis. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:2123 / 2129
页数:7
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