Aymard G, Cayre-Castel M, Fernandez C, Lacomblez L, Diquet B
Laboratoire de Pharmacocinétique, Hôpital Pitié-Salpêtrière, Assistance-Publique des Hôpitaux de Paris, France.
Ther Drug Monit. 1998 Aug;20(4):422-9. doi: 10.1097/00007691-199808000-00012.
A new high-performance liquid chromatography (HPLC) assay was developed for the simultaneous determination of tacrine (THA), nimodipine, and their three metabolites (MI, MII, and MIII) using a 1-ml plasma sample volume. A liquid-liquid extraction procedure was coupled with a reverse-phase HPLC separation. Quantification was performed by fluorometric detection for THA and metabolites and by ultraviolet detection for nimodipine and metabolites. Peak-height ratios were linear across the ranges 0.5 to 100 micro/l for THA and its three metabolites; 2 to 500 microg/l for nimodipine, MII, and MIII; and 4 to 500 microg/l for MI. Correlation coefficients were better than 0.998 for all compounds. Accuracy and precision were less than 12% for the entire concentration range for each substance. This method is sensitive and selective. Analysis of plasma samples collected from patients with Alzheimer disease demonstrated that the assay is suitable for clinical and pharmacokinetic trials including drug-drug interactions studies.
建立了一种新的高效液相色谱（HPLC）测定法，用于同时测定他克林（THA）、尼莫地平及其三种代谢物（MI、MII和MIII），血浆样本体积为1 ml。液-液萃取程序与反相HPLC分离相结合。通过荧光检测对THA及其代谢物进行定量，通过紫外检测对尼莫地平和代谢物进行定量。THA及其三种代谢物的峰高比在0.5至100微克/升范围内呈线性；尼莫地平、MII和MIII为2至500微克/升；MI为4至500微克/升。所有化合物的相关系数均优于0.998。每种物质在整个浓度范围内的准确度和精密度均小于12%。该方法灵敏且具有选择性。对阿尔茨海默病患者采集的血浆样本进行分析表明，该测定法适用于包括药物相互作用研究在内的临床和药代动力学试验。
