Lai W K, Pang C P, Law L K, Wong R, Li C K, Yuen P M
Department of Chemical Pathology, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
Clin Chem. 1998 Dec;44(12):2506-10.
Busulfan (BU) is a widely used alkylating agent for antineoplastic therapy and marrow ablation in preparation for bone marrow transplantation (BMT). High-dose BU often leads to successful preparation and low relapse but is associated with veno-occlusive disease of liver. We established a protocol to determine postdosage plasma BU concentrations by gas chromatography-mass fragmentography in an attempt to relate clinical outcome to plasma BU concentrations. We used nonisotopic pusulfan as the internal standard. After extraction into ethyl acetate, BU and pusulfan were iodinated into 1, 4-diiodobutane and 1,5-diiodopentane, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis was carried out on an Hewlett-Packard (HP) 5890II gas chromatograph with a 30-m 100% methyl silicon narrow bore, fused-silica capillary column interfaced with an HP 5970A mass spectrometer. Helium was the carrier gas. The sample molecules were identified by total ion monitoring and quantified by selective ion monitoring of m/z 183 and 197. The calibration curve was linear to 4 mg/L. The limit of quantification was 0.04 mg/L, and the analytical recovery was approximately 97%. The within-day and between-day imprecision (CV) was <6% and 9%, respectively. In a preliminary study of 12 children, the BU areas under the BU-time curve were 616-949 micromol. min/L after the first dose and 793-1143 micromol. min/L after the fifth dose. We conclude that the GC-MS procedure is suitable for routine analysis of plasma BU.
白消安（BU）是一种广泛用于抗肿瘤治疗和骨髓消融以准备进行骨髓移植（BMT）的烷化剂。高剂量白消安通常能成功完成预处理且复发率低，但与肝静脉闭塞病有关。我们建立了一种通过气相色谱 - 质谱碎片分析法测定给药后血浆白消安浓度的方案，试图将临床结果与血浆白消安浓度相关联。我们使用非同位素的普舒凡作为内标。萃取到乙酸乙酯中后，白消安和普舒凡分别被碘化为1,4 - 二碘丁烷和1,5 - 二碘戊烷。气相色谱 - 质谱（GC - MS）分析在配备30米100%甲基硅窄孔熔融石英毛细管柱的惠普（HP）5890II气相色谱仪上进行，该色谱柱与HP 5970A质谱仪相连。氦气作为载气。通过全离子监测鉴定样品分子，并通过对m/z 183和197的选择性离子监测进行定量。校准曲线在4 mg/L范围内呈线性。定量限为0.04 mg/L，分析回收率约为97%。日内和日间不精密度（CV）分别<6%和9%。在对12名儿童的初步研究中，首次给药后白消安 - 时间曲线下面积为616 - 949微摩尔·分钟/升，第五次给药后为793 - 1143微摩尔·分钟/升。我们得出结论，GC - MS方法适用于血浆白消安的常规分析。
