Stability of Busulfan in Frozen Plasma and Whole Blood Samples

Abstract

Busulfan is widely used as a component of myeloablative conditioning therapy for bone marrow transplantation (1)(2)(3)(4)(5). Busulfan is most often used at a fixed total dose of 16 mg/kg. Wide interindividual variation in the bioavailability of busulfan has been recognized. Pharmacokinetic analyses to achieve target plasma concentrations and dose adjustments are increasingly being used to improve the outcome of bone marrow transplantation (6)(7)(8). Studies on busulfan kinetics have demonstrated that busulfan concentrations in stored plasma samples are stable for up to 3 months at −20 °C and that blood samples for busulfan analysis should be centrifuged within 3 h of collection and plasma frozen if not analyzed immediately (9)(10)(11). The stability of busulfan in blood and plasma samples stored for longer time periods and at lower temperatures has not been reported. Because pharmacokinetic analysis of busulfan requires collection of multiple samples at frequent intervals, such data will be useful in planning transport and analysis of blood and plasma samples. This study was undertaken to determine the stability of busulfan in whole blood samples stored up to 24 h at 4 °C and in plasma samples stored up to 2 years at −80 °C. Busulfan analysis was performed on plasma samples by HPLC as described previously (12). Briefly, busulfan in plasma was extracted with toluene and derivatized with 1 mol/L tetrafluorothiophenol …