Method development aspects for the quantitation of pharmaceutical compounds in human plasma with a matrix-assisted laser desorption/ionization source in the multiple reaction monitoring mode

被引:45
作者
Kovarik, Peter
Grivet, Chantal
Bourgogne, Emmanuel
Hopfgartner, Gerard
机构
[1] Univ Geneva, Life Sci Mass Spectrometry, Sch Pharmaceut Sci, Univ Lausanne, CH-1211 Geneva 4, Switzerland
[2] MDS Sciex, Concord, ON, Canada
关键词
D O I
10.1002/rcm.2912
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The present work investigates various method development aspects for the quantitative analysis of pharmaceutical compounds in human plasma using matrix-assisted laser desorption/ionization and multiple reaction monitoring (MALDI-MRM). Talinolol was selected as a model analyte. Liquid-liquid extraction (LLE) and protein precipitation were evaluated regarding sensitivity and throughput for the MALDI-MRM technique and its applicability without and with chromatographic separation. Compared to classical electrospray liquid chromatography/mass spectrometry (LC/ ESI-MS) method development, with MALDI-MRM the tuning of the analyte in single MS mode is more challenging due to interfering matrix background ions. An approach is proposed using background subtraction. With LLE and using a 200 mu L human plasma aliquot acceptable precision and accuracy could be obtained in the range of 1 to 1000 ng/mL without any LC separation. Approximately 3 s were required for one analysis. A full calibration curve and its quality control samples (20 samples) can be analyzed within 1 min. Combining LC with the MALDI analysis allowed improving the linearity down to 50 pg/mL, while reducing the throughput potential only by two-fold. Matrix effects are still a significant issue with MALDI but can be monitored in a similar way to that used for LC/ESI-MS analysis. Copyright (c) 2007 John Wiley & Sons, Ltd.
引用
收藏
页码:911 / 919
页数:9
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