Embree L, Burns R B, Heggie J R, Phillips G L, Reece D E, Spinelli J J, Hartley D O, Hudon N J, Goldie J H
Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Cancer Chemother Pharmacol. 1993;32(2):137-42. doi: 10.1007/BF00685617.
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 63Ni electron-capture detector provided a limit of detection of 0.0600 microgram/ml with a limit of quantitation of 0.100 microgram/ml busulfan in biological samples. Calibration curves were linear from 0.100 to 3.00 micrograms/ml in plasma (500 microliters) and 0.100 to 2.00 micrograms/ml in plasma ultrafiltrate (100 microliters). 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.
本文报道了一种用于药代动力学研究的气相色谱法的开发与验证，该方法可测定人血浆中总白消安和游离白消安的浓度。合成了内标物1,6-双（甲磺酰氧基）己烷以及一种潜在代谢物3-羟基环丁砜。含有白消安和内标的血浆及血浆超滤液样品用乙酸乙酯萃取，并在气相色谱测定前用2,3,5,6-四氟硫酚进行衍生化。63Ni电子捕获检测器对生物样品中白消安的检测限为0.0600微克/毫升，定量限为0.100微克/毫升。血浆（500微升）中校准曲线在0.100至3.00微克/毫升范围内呈线性，血浆超滤液（100微升）中在0.100至2.00微克/毫升范围内呈线性。萃取率和衍生化率分别为78.4%至89.6%和56.0%至71.3%。证明了该方法在其潜在代谢物存在下对白消安的特异性。此外，含有共同给药药物的血浆样品在这些条件下无响应。口服1毫克/千克白消安剂量后获得的临床样品证明了该方法在分析血浆总浓度和游离浓度方面的适用性。
