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Simultaneous determination of prochlorperazine and its metabolites in human plasma using isocratic liquid chromatography tandem mass spectrometry

Authors

  • Masaki Tashiro,

    1. Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
    2. Department of Clinical Pharmaceutics and Pharmacy Practice, Faculty of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Shizuoka, Japan
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  • Takafumi Naito,

    1. Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
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  • Yoshiyuki Kagawa,

    1. Department of Clinical Pharmaceutics and Pharmacy Practice, Faculty of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Shizuoka, Japan
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  • Junichi Kawakami

    Corresponding author
    • Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
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J. Kawakami, Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431–3192, Japan. E-mail: kawakami-ham@umin.ac.jp

ABSTRACT

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.

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