UPLC-Tandem Mass Spectrometry for Quantification of Busulfan in Human Plasma: Application to Therapeutic Drug Monitoring

Busulfan (Bu) is an alkylating agent commonly used in preparative regimens for hematologic malignant and non-malignant patients undergoing hematopoietic stem cell transplantation (HSCT). The objective of the present study was to develop an UPLC-MS/MS method for quantification of Bu in human plasma. A total of 55 patients with hematologic malignancies (n = 34) and non- malignancies (n = 21) received myeloablative Bu therapy prior to HSCT. A tandem mass spectrometric method was developed and validated to quantify Bu levels in these patients. The method was fully validated over the concentration range of 25–2000 ng/mL ( r > 0.99). The assay method demonstrated good precision and accuracy. Stability studies indicated that the drug was stable in various conditions. Incurred sample reanalysis findings were within acceptable ranges (