Quantification of busulfan in plasma by liquid chromatography-ion spray mass spectrometry - Application to pharmacokinetic studies in children

Optimisation of busulfan dosage in patients undergoing bone marrow transpla ntation is recommended in order to reduce toxic effects associated with hig h drug exposure. A new method was developed coupling liquid chromatography with mass spectrometry (LC-MS) and was validated for the determination of b usulfan concentrations in plasma. Recovery was 86.7%, the limit of detectio n was 2.5 ng/ml and linearity ranged from 5 to 2500 ng/mL The correlation b etween the busulfan concentrations measured by our previously published HPL C-UV method and the new HPLC-MS method was highly significant (P <0.0001). Sample volume was reduced and the method was rapid, sensitive and less expe nsive than the methods previously used in our laboratory. This method was u sed to determine the pharmacokinetic parameters of busulfan after the first administration of 1 mg/kg orally, in 13 children receiving the drug as par t of the preparative regimen for bone marrow transplantation. Our results w ere similar to previously reported data. They showed that the apparent oral clearance of busulfan was 0.299 +/-0.08 l/h/kg, and that it was significan tly higher (P=0.02) in patients below the age of 5 years than in older chil dren. (C) 2001 Elsevier Science B.V. All rights reserved.