High-performance liquid chromatography tandem mass spectrometry procedure with automated solid phase extraction sample preparation for the quantitative determination of paclitaxel (Taxol®) in human plasma

被引:0
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作者
Sottani, C
Minoia, C
D'Incalci, M
Paganini, M
Zucchetti, M
机构
[1] S Maugeri Fdn, Lab Environm Hyg & Ind Toxicol, Pavia, Italy
[2] Mario Negri Inst Pharmacol Res, Dept Oncol, Lab Canc Pharmacol, I-20157 Milan, Italy
关键词
D O I
10.1002/(SICI)1097-0231(19980314)12:5<251::AID-RCM145>3.0.CO;2-Z
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A sensitive, specific, accurate and reproducible analytical method was developed and validated for the quantitation of the anticancer agent paclitaxel in human plasma, This procedure is based on high performance liquid chromatography/ion spray - tandem mass spectrometry. This methodology is highly specific because a MS/MS technique (multiple reactant-ion monitoring, MRM) was used for both paclitaxel and its internal standard, The use of a fully automated solid phase extraction procedure, using a CN Sep-pak cartridge, to improve the detection limit and quantification limit of paclitaxel in human plasma samples, was evaluated, The method involves the addition of methyl-paclitaxel as internal standard (I.S.). The retention times of paclitaxel and the I.S. were 2.8 and 4.0 min., respectively, The assay was linear over the range 5 to 500 ng/mL, with a quantification limit of 5 ng/mL having a coefficient of variation (C.V.) <10%. Standard calibration curves, performed on three different days, had correlation coefficients always greater than 0.998, The intra and inter-day precision were within 12%, and accuracy was included in the range 102-110%. Paclitaxel recovery assessed at 15,250 and 500 ng/mL, was determined to be greater than 85%. The assay is applicable to clinical pharmacokinetic studies. (C) 1998 John Wiley & Sons, Ltd.
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页码:251 / 255
页数:5
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