Yonekawa W D, Kapetanovic I M, Kupferberg H J, Paanakker J E, van de Laar G L
J Chromatogr. 1986 Apr 25;377:205-12. doi: 10.1016/s0378-4347(00)80775-6.
We have developed a sensitive and accurate method for the determination in plasma of the antiepileptic drug dl-(5 alpha,9 alpha,11S*)-5,6,9,10- tetrahydro-N,N-dimethyl-5,9-methanobenzocycloocten-11-amine hydrochloride and its N-desmethyl metabolite. The extraction procedure utilizes base-treated disposable C2 solid-phase columns, with the analyte eluted with organic solvent. Nitrogen-selective gas chromatography is used for detection. Linear regression analysis showed that the method is linear between 4 and 1500 ng/ml for the parent drug and between 8 and 3000 ng/ml for the N-desmethyl metabolite. Intra- and inter-day variability, as shown by the coefficient of variation, is less than 8% for both compounds. The method is applicable to routine plasma determination of both these compounds in clinical pharmacokinetic studies.
我们已经开发出一种灵敏且准确的方法,用于测定血浆中的抗癫痫药物dl-(5α,9α,11S*)-5,6,9,10-四氢-N,N-二甲基-5,9-亚甲基苯并环辛烯-11-胺盐酸盐及其N-去甲基代谢物。提取过程采用经碱处理的一次性C2固相柱,用有机溶剂洗脱分析物。采用氮选择性气相色谱法进行检测。线性回归分析表明,该方法对于母体药物在4至1500 ng/ml之间呈线性,对于N-去甲基代谢物在8至3000 ng/ml之间呈线性。两种化合物的日内和日间变异性(以变异系数表示)均小于8%。该方法适用于临床药代动力学研究中对这两种化合物进行常规血浆测定。