Cano J P, Sumirtapura Y C, Cautreels W, Sales Y
J Chromatogr. 1981 Dec 11;226(2):413-22. doi: 10.1016/s0378-4347(00)86075-2.
A gas chromatographic assay with electron-capture detection (GC--EC) is described for the metabolites of ethyl loflazepate (Victan), a new benzodiazepine with a potent anti-anxiety activity, in biological fluids. Since the parent drug undergoes a first-pass effect, pharmacokinetic data may only be obtained by measuring the total levels of two of the major metabolites. Accurate data can not be obtained for the metabolites separately since one of them (M1) is chemically transformed to the other (M2) during plasma sampling, storage and extraction. A sensitive, specific and accurate GC--EC assay is developed using a synthetic analogue of M2 as an internal standard. The limit of detection in plasma is approximately 2 ng/ml and the precision about 3% (within-run and between-run). The method is applied to plasma samples collected after oral administration of 2 mg and 4 mg of the drug in tablet form to human volunteers. The results obtained are correlated with those from an existing gas chromatographic--mass spectrometric assay. A very good correlation between the results (inter-laboratory comparison) is obtained, validating both techniques.
本文描述了一种采用电子捕获检测的气相色谱分析法（GC-EC），用于测定生物体液中新型具有强效抗焦虑活性的苯二氮䓬类药物氯氟卓乙酯（Victan）的代谢产物。由于母体药物会经历首过效应，因此只能通过测量两种主要代谢产物的总水平来获取药代动力学数据。由于其中一种代谢产物（M1）在血浆采样、储存和提取过程中会化学转化为另一种代谢产物（M2），所以无法分别获得这两种代谢产物的准确数据。使用M2的合成类似物作为内标，开发了一种灵敏、特异且准确的GC-EC分析法。血浆中的检测限约为2 ng/ml，精密度约为3%（批内和批间）。该方法应用于给人类志愿者口服2 mg和4 mg片剂形式的药物后采集的血浆样本。将所得结果与现有气相色谱-质谱分析法的结果进行关联。结果之间获得了非常好的相关性（实验室间比较），验证了这两种技术。
