Rapid determination of the anti-cancer drug melphalan (Alkeran (TM)) in human serum and plasma by automated solid phase extraction and liquid chromatography tandem mass spectrometry

A bioanalytical method for the determination of the anticancer drug Melphal an (Alkeran(TM)) in human serum and plasma is described. Automated solid ph ase extraction of the analyte is carried out with C18 sorbent pac ked in a 96 well format microtitre plate using a robotic sample processor. The extra cts are analysed by isocratic reversed phase liquid chromatography using pn eumatically and thermally assisted electrospray ionisation (TurbolonSpray(T M)) with selected reaction monitoring. The method is specific and sensitive , with a range of 2-400 ng mL(-1) in human serum and plasma for Melphalan ( sample volume 200 muL). The method is accurate and precise with intra-assay and inter-assay precision (%CV) of <15% and bias <15%. The automated extra ction procedure is significantly faster than manual sample pretreatment met hods: a batch of 96 samples is extracted in 50 minutes, allowing for faster sample turnaround. The method has been used to provide pharmacokinetic sup port to biocomparability studies of Alkeran(TM) following single doses of o ral tablet formulations.