Simultaneous determination of prochlorperazine and its metabolites in human plasma using isocratic liquid chromatography tandem mass spectrometry
Article first published online: 12 OCT 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Volume 26, Issue 6, pages 754–760, June 2012
How to Cite
Tashiro, M., Naito, T., Kagawa, Y. and Kawakami, J. (2012), Simultaneous determination of prochlorperazine and its metabolites in human plasma using isocratic liquid chromatography tandem mass spectrometry. Biomed. Chromatogr., 26: 754–760. doi: 10.1002/bmc.1725
- Issue published online: 1 MAY 2012
- Article first published online: 12 OCT 2011
- Manuscript Accepted: 29 AUG 2011
- Manuscript Revised: 12 AUG 2011
- Manuscript Received: 12 MAY 2011
- cancer patient
Oral prochlorperazine (PCZ), an antiemetic, undergoes extensive first-pass metabolism. The study developed a simultaneous analytical method for PCZ and its major metabolites, prochlorperazine sulfoxide (PCZSO), N-demethylprochlorperazine (NDPCZ) and 7-hydroxyprochlorperazine (PCZOH), in human plasma using an isocratic liquid chromatography–tandem mass spectrometry (LC-MS/MS) method. Deproteinized plasma specimens were separated using a 3 µm particle size octadecylsilyl column, and the run time was 10 min. The calibration curves were linear over the concentration ranges of 0.01–40 µg/L for PCZ, NDPCZ and PCZOH, and 0.05–80 µg/L for PCZSO. The intra- and inter-assay precisions and accuracies were within 7.0 and 99–104% and within 9.0 and 99–105%, respectively. The lower limits of quantification in human plasma were 10 ng/L for PCZ, NDPCZ and PCZOH, and 50 ng/L for PCZSO. The validated method was applied to the determination of plasma samples in 37 cancer patients receiving PCZ. Large interindividual variations were observed in plasma concentrations of PCZ, PCZSO, NDPCZ and PCZOH (relative standard deviation, 89.4, 88.7, 86.4 and 78.2%, respectively). In conclusion, this simultaneous LC-MS/MS method with acceptable analytical performance can be helpful for evaluating the pharmacokinetics of PCZ, including the determination of its metabolites in cancer patients and in clinical research. Copyright © 2011 John Wiley & Sons, Ltd.