Simultaneous determination of capecitabine and its metabolites by HPLC and mass spectrometry for preclinical and clinical studies.
A reverse-phase high-performance liquid chromatography method with electrospray ionization and detection by mass spectrometry is described for the simultaneous determination of capecitabine, its intermediate metabolites (DFCR, DFUR) and the active metabolite 5-fluorouracil in mouse plasma, liver and human xenograft tumours. The method was also cross-validated in human plasma and human tumour for clinical application. The method has greater sensitivity than previously published methods with an equivalent accuracy and precision. It uses less biological material (plasma, tissue) and should therefore be applicable to biopsies in patients treated with capecitabine.
Guichard
Sylvie M
SM
Pharmacology and Drug Development Team, Cancer Research UK Centre, University of Edinburgh, Crewe Road, Edinburgh EH4 2XR, UK. Sylvie.guichard@cancer.org.uk
Mayer
Iain
I
Jodrell
Duncan I
DI
D000818:Animals; D000069287:Capecitabine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015179:Colorectal Neoplasms / Q000737:chemistry; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D004355:Drug Stability; D005467:Floxuridine / Q000032:analysis; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008099:Liver / Q000737:chemistry; D051379:Mice; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D005467:Floxuridine; D003841:Deoxycytidine; D000069287:Capecitabine; C418208:5'-deoxy-5-fluorocytidine; D005472:Fluorouracil; C025034:doxifluridine