Quantification of busulfan in plasma by gas chromatography-mass spectrometry following derivatization with tetrafluorothiophenol.
A specific and highly sensitive method has been developed for the determination of busulfan in plasma by gas chromatography-mass spectrometry using a deuterium-labeled busulfan (busulfan-d8) as internal standard. Plasma containing busulfan and busulfan-d8 were extracted with ethyl acetate and derivatized with 2,3,5,6-tetrafluorothiophenol prior to the monitoring of specific ions. The limit of quantification of the assay was 20 ng/ml and the calibration curve was linear over the range of 10 to 2000 ng/ml of derivatized busulfan. This method was in good agreement with the GC-MS assay using derivatization with sodium iodide and measuring diiodobutane. In addition, a pharmacokinetic study of busulfan was conducted in six children. The apparent oral clearance was 5.7+/-1.9 ml/kg/min and the volume of distribution was 1.0+/-0.4 l/kg and were similar to those previously reported in pediatric patients.
Quernin
M H
MH
Pediatric Clinical Pharmacology, Hôpital Robert Debré, Paris, France.
Poonkuzhali
B
B
Montes
C
C
Krishnamoorthy
R
R
Dennison
D
D
Srivastava
A
A
Vilmer
E
E
Chandy
M
M
Jacqz-Aigrain
E
E
D000477:Alkylating Agents / Q000097:blood* / Q000493:pharmacokinetics; D002066:Busulfan / Q000097:blood* / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D010636:Phenols; D012680:Sensitivity and Specificity; D012974:Sodium Iodide; D013438:Sulfhydryl Compounds
D000477:Alkylating Agents; D010636:Phenols; D013438:Sulfhydryl Compounds; C081141:2,3,5,6-tetrafluorobenzenethiol; D012974:Sodium Iodide; D002066:Busulfan