High-performance liquid chromatographic assay for cytosine arabinoside, uracil arabinoside and some related nucleosides.

A novel, dual-column high-performance liquid chromatographic method for determination of the anti-cancer drug cytosine arabinoside (Ara-C) and its major metabolite uracil arabinoside (Ara-U) has been developed. The analytical procedure is sensitive (25 ng/ml) and specific for Ara-C, Ara-U and the endogenous nucleosides that may influence response to Ara-C therapy, cytidine and deoxycytidine. Conventional and high dose calibration curves were linear and the method precise with the assay coefficient of variation for Ara-C and Ara-U not greater than 9.1% over the range of 0.1-10 micrograms/ml. Accuracy was determined to be within +/- 3 to 9% over this concentration range. Using this method, patient plasma samples from both conventional dose (100-200 mg/m2 per day) and high dose (3500-6500 mg/m2 per day) Ara-C can be simultaneously analyzed for Ara-C, Ara-U and nucleosides so that comparative pharmacokinetic and pharmacodynamic studies can be conducted.