Mellström B, Tybring G
J Chromatogr. 1977 Nov 1;143(6):597-605. doi: 10.1016/s0378-4347(00)81314-6.
A method for the determination of chlorimipramine and its metabolite demethylchlorimipramine in the plasma of depressed patients during treatment is described. The method involves extraction of the parent drug, its metabolite and the internal standard from plasma, back-extraction into an acidic aqueous phase and re-extraction into a small volume of organic phase. Separation and quantitation are carried out by ion-pair partition chromatography with UV detection. Accurate determination if possible down to levels of 30 and 60 nmole per liter of plasma for chlorimipramine and the metabolite, respectively, when 1 ml of plasma is used. The coefficient of variation is 7.3% or less at different levels for chlorimipramine and demethylchlorimipramine. Plasma levels of the parent drug and the metabolite measured by this liquid chromatographic method and by a gas chromatographic procedure with electron-capture detection were in good agreement (r = 0.98). The steady-state plasma level of the metabolite was always higher than that of the parent drug in the 34 depressed patients investigated. The mean ratio between the metabolite and the parent drug was 2.7 +/- 1.1 (S.D.) Large inter-individual differences in the levels of the two compounds in patients receiving similar doses were found.
本文描述了一种在抑郁症患者治疗期间测定其血浆中氯米帕明及其代谢产物去甲基氯米帕明的方法。该方法包括从血浆中提取母体药物、其代谢产物和内标，反萃取到酸性水相中，再萃取到少量有机相中。通过离子对分配色谱法和紫外检测进行分离和定量。当使用1ml血浆时，分别测定氯米帕明及其代谢产物，可准确测定至血浆中每升30和60纳摩尔的水平。氯米帕明和去甲基氯米帕明在不同水平下的变异系数为7.3%或更低。用这种液相色谱法和带电子捕获检测的气相色谱法测得的母体药物和代谢产物的血浆水平吻合良好（r = 0.98）。在所研究的34例抑郁症患者中，代谢产物的稳态血浆水平总是高于母体药物。两种化合物在接受相似剂量的患者中的水平存在较大的个体差异。
