人血浆中尼莫地平的毛细管气相色谱电子捕获检测法及药代动力学

DETERMINATION OF NIMODIPINE AND ITS PHARMACOKINETICS IN HUMAN PLASMA BY CAPILLARY GAS CHROMATOGRAPHY USING ELECTRON CAPTURE DETECTION

目的：建立测定人血浆中尼莫地平的毛细管气相色谱电子捕获检测法，并用本法研究尼莫地平片剂在健康人体内的药代动力学及相对生物利用度。方法：色谱柱为２５ｍ×０２ｍｍＩＤＯＶ１０１熔融石英毛细管柱，检测器为６３Ｎｉ电子捕获检测器。内标为尼群地平，血浆样品在碱性条件下用正己烷—乙酸乙酯（１∶１）提取。结果：浓度在２０～１５００ｎｇ·ｍｌ－１与峰面积比呈良好线性关系，γ＝０９９９８９。人血浆中尼莫地平的最低检出浓度为０１ｎｇ·ｍｌ－１，方法重现性好，提取回收率大于８０％。１０名志愿者随机交叉口服单剂量１００ｍｇ二种国产尼莫地平片剂后，以本法测定其体内过程符合一室模型。二种片剂的ＡＵＣ０→∞。Ｃｍａｘ，Ｔｍａｘ均无显著差异。结论：尼莫地平血药浓度测定结果表明两种尼莫地平片剂生物等效，Ａ片剂对Ｂ片剂的相对生物利用度为１０２０％。

AIM: To develope a capillary GC ECD method for the study of phamacokinetics and relative bioavailability of nimodipine tablet in human body. METHODS: Chromatography was performed on a 25 m×0 2 mm ID 0 2 μm film thickness OV 101 fused silica capillary column coupled with a 63 Ni electron capture detector. The carrier gas was highly pure nitrogen. The flow rate of carrier gas in the capillary column was 1 8 ml·min -1 . The split ratio was 1∶33. The flow rate of make up gas was 17 ml·min -1 . The temperatures of the column, injector and detector were 260℃, 270℃ and 300℃, respectively. The internal standard was nitrendipine. After making alkaline with 1 mol·L -1 NaOH solution, the plasma was extracted with n hexane ethyl acetate (1∶1). RESULTS: A good linearity was obtained from 2 0 ng·ml -1 to 150 0 ng·ml -1 of nimodipine in human plasma with a correlation coefficient of 0 99989. The detection limit of nimodipine in human plasma was 0 1 ng·ml -1 . The extraction recovery was more than 80%. The pharmacokinetics of nimodipine was determined by this GC ECD method following a single oral dose of 100 mg of two kinds of domestic nimodipine tablets given to each of 10 volunteers in an open randomized two way crossover design. The results showed that the plasma concentration time courses of the two kinds of tablets conformed to one compartment model. There was no significant difference between the two formulations in the AUC 0→∞ , C max and T max . CONCLUSION: The established GC ECD method was found to be a good method for determination of nimodipine in human plasma. The results of statistical analysis showed that the two formulations of nimodipine were biologically equivalent. The relative bioavailability of tablet A was 102 0% compared with that of tablet B.