Quantitative analysis of the experimental cytotoxic drug cyclopentenyl cytosine and its metabolite in plasma with HPLC tandem mass spectrometry.
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 microm 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 microM 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.
Schimmel
Kirsten
K
Leiden University Medical Center, Department of Clinical Pharmacy and Toxicology, Leiden, The Netherlands. k.j.m.schimmel@lumc.nl
van Lenthe
Henk
H
Leen
Rene
R
Kulik
Willem
W
Verschuur
Arnauld
A
Guchelaar
Henk-Jan
HJ
van Kuilenburg
André
A
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003562:Cytidine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014498:Uracil / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry / Q000378:metabolism
D014498:Uracil; D003562:Cytidine; C045911:cyclopentenyl cytosine; C068989:cyclopentenyluracil