Greenblatt D J, Franke K, Shader R I
J Chromatogr. 1978 Sep 1;146(2):311-20.
This paper describes a rapid and sensitive method for analysis of lorazepam and its glucuronide metabolite in plasma and urine following therapeutic doses of lorazepam in humans. After addition of the structurally related benzodiazepine derivative, oxazepam, as the internal standard, 1-ml samples of plasma or urine are extracted twice at neutral pH with benzene (containing 1.5% isoamyl alcohol). The combined extracts are evaporated to dryness, reconstituted, and subjected to gas chromatographic analysis using a 3% OV-17 column and an electron-capture detector. Lorazepam glucuronide in urine is similarly analyzed following enzymatic cleavage with Glusulase. The sensitivity limits are 1--3 ng of analyzed following enzymatic cleavage with Glusulase. The sensitivity limits are 1--3 ng of lorazepam per ml of original sample, and the variability of identical samples is 5% or less. The applicability of the method to pharmacokinetic studies of lorazepam is demonstrated.
本文描述了一种快速灵敏的方法，用于分析人体服用治疗剂量劳拉西泮后血浆和尿液中劳拉西泮及其葡萄糖醛酸代谢物。加入结构相关的苯二氮䓬衍生物奥沙西泮作为内标后，取1 ml血浆或尿液样品，在中性pH条件下用含1.5%异戊醇的苯萃取两次。合并萃取液蒸发至干，重新溶解，然后使用3% OV - 17柱和电子捕获检测器进行气相色谱分析。尿液中的劳拉西泮葡萄糖醛酸经葡糖醛酸酶酶解后同样进行分析。灵敏度限值为每毫升原始样品中劳拉西泮1 - 3 ng，相同样品的变异度为5%或更低。该方法在劳拉西泮药代动力学研究中的适用性得到了验证。
