Simultaneous determination of capecitabine and its metabolite 5‐fluorouracil by column switching and liquid chromatographic/tandem mass spectrometry

A liquid chromatographic/tandem mass spectrometric method was developed and validated for the quantitation of capecitabine and its metabolite 5‐fluorouracil in human plasma. The simultaneous determination of both analytes was achieved by a column switching method using a trapping column and two analytical columns with different stationary phases. Isocratic elution was used for the separation of capecitabine on a C 18 column whereas 5‐fluorouracil was separated using gradient elution on an non‐polar carbon phase. The calibration curves were linear for both compounds with a correlation factor ( R 2 ) > 0.9993 for 5‐fluorouracil and >0.9942 for capecitabine. The assay was validated in the concentration range 5.00–1000 ng ml −1 for both compounds. The intra‐day precision was better than 10% for 5‐fluorouracil and better than 11% for capecitabine whereas the inter‐day precision was better than 8% for 5‐fluorouracil and better than 14% for capecitabine. Copyright © 2004 John Wiley & Sons, Ltd.