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Quantitative analysis of the experimental cytotoxic drug cyclopentenyl cytosine and its metabolite in plasma with HPLC tandem mass spectrometry
Author(s) -
Schimmel Kirsten,
Lenthe Henk van,
Leen Rene,
Kulik Willem,
Verschuur Arnauld,
Guchelaar HenkJan,
Kuilenburg André van
Publication year - 2008
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1067
Subject(s) - chemistry , chromatography , tandem mass spectrometry , electrospray ionization , metabolite , mass spectrometry , high performance liquid chromatography , pharmacokinetics , quantitative analysis (chemistry) , detection limit , pharmacology , biochemistry , medicine
Abstract The cytotoxic drug cyclopentenyl cytosine (CPEC) is currently being investigated in early clinical trials. Monitoring of plasma levels is required for pharmacokinetic analysis and management of toxicity. This paper describes the analysis of CPEC and cyclopentenyl uracil (CPEU) in plasma by HPLC–electrospray ionization tandem mass spectrometry. The calibration curves for CPEC and the metabolite CPEU were linear up to 10 µ m with correlation coefficients of 0.997 (SD = 0.002, n = 10) and 0.997 (SD = 0.004, n = 10), respectively. The detection limit for CPEC was 0.03 and 0.12 µ m for CPEU. The intra‐ and interassay coefficients of variation for CPEC and CPEU were less then 10%. The usefulness of the method was demonstrated by analyzing CPEC and CPEU in plasma of a patient treated with CPEC. HPLC with electrospray ionization tandem mass spectrometry allowed rapid and sensitive determination of CPEC and CPEU levels in plasma. Copyright © 2008 John Wiley & Sons, Ltd.