GAS-CHROMATOGRAPHIC ANALYSIS OF BUSULFAN FOR THERAPEUTIC DRUG-MONITORING

被引:28
作者
EMBREE, L
BURNS, RB
HEGGIE, JR
PHILLIPS, GL
REECE, DE
SPINELLI, JJ
HARTLEY, DO
HUDON, NJ
GOLDIE, JH
机构
[1] UNIV BRITISH COLUMBIA,FAC PHARMACEUT SCI,DIV PHARMACEUT CHEM,VANCOUVER V6T 1W5,BC,CANADA
[2] VANCOUVER GEN HOSP,BRITISH COLUMBIA CANC AGCY,DIV HEMATOL,VANCOUVER V5Z 1M9,BC,CANADA
[3] UNIV BRITISH COLUMBIA,FAC MED,VANCOUVER V6T 1W5,BC,CANADA
关键词
BUSULFAN; THERAPEUTIC DRUG MONITORING; ANALYSIS;
D O I
10.1007/BF00685617
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The development and validation of a gas chromatographic assay method for determination of total and free busulfan concentrations in human plasma for pharmacokinetic studies is reported. 1,6-Bis(methanesulfonyloxy)hexane, the internal standard, and a potential metabolite, 3-hydroxysulfolane, were synthesized. Plasma and plasma ultrafiltrate samples containing busulfan and internal standard were extracted with ethyl acetate and derivatized with 2,3,5,6-tetrafluorothiophenol prior to gas chromatographic determination. The Ni-63 electron-capture detector provided a limit of detection of 0.0600 mug/ml with a limit of quantitation of 0.100 mug/ml busulfan in biological samples. Calibration curves were linear from 0.100 to 3.00 mug/ml in plasma (500 mul) and 0.100 to 2.00 mug/ml in plasma ultrafiltrate (100 mul). Extraction and derivatization yields ranged from 78.4% to 89.6% and 56.0% to 71.3%, respectively. Specificity of this assay for busulfan in the presence of its potential metabolites was demonstrated. Also, plasma samples containing co-administered drugs gave no response under these conditions. Clinical samples obtained following administration of a 1 mg/kg oral busulfan dose demonstrate the applicability of this method to analysis of total and free plasma concentrations.
引用
收藏
页码:137 / 142
页数:6
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