Measurement of plasma busulfan concentration by high-performance liquid chromatography with ultraviolet detection

Busulfan is widely used in bone marrow transplantation. Increased area under the plasma concentration curve has been shown to correlate with venoocclusive disease, which occurs in approximately 20% of these patients. The authors developed a high performance liquid chromatography assay for the determination of plasma busulfan concentration using ultraviolet detection and a single-step derivatization and extraction. The absolute retention times of busulfan and the internal standard were 2.8 and 5.6 min, respectively. The assay possessed linearity up to 200 mumol/l, sensitivity to at least 0.2 mumol/l, average recovery of 101%, and run-to-run precision (n = 34) of < 7%. Furthermore, the assay proved to be free of interference from 59 medications and correlated highly with a validated method employing gas chromatography with electron capture detection (slope = 0.90, intercept = 0.17, r = 0.98, n = 31). The authors conclude that the method described here is ideally suited for the therapeutic monitoring of busulfan.