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目的：建立单步萃取反相高效液相色谱法测定人全血中环孢菌素Ａ（ＣｙＡ）浓度，研究该药物在人体内的药动学和生物利用度。方法：血样经乙醚单步萃取后，以Ｃ８硅胶键合相为固定相，乙腈甲醇水异丙醇（５７∶１８∶２５∶１．５）为流动相，６５℃柱温下进行色谱分离。采用环孢菌素Ｄ为内标，在２０８ｎｍ处紫外定量检测。所得数据采用ＰＫＢＰＮ１药动学程序拟合计算，求出有关药动学参数。结果：ＣｙＡ血浓度在４０～１２００ｎｇ·ｍｌ－１范围内与色谱峰面积比值呈良好的线性关系，全血中ＣｙＡ最低检测浓度为２０ｎｇ·ｍｌ－１，日内（ｎ＝７）及日间（ｎ＝６）测定ＲＳＤ为４．８％及７．８％，，方法回收率为９８．６％～９９．５％。对１０名青年男性正常者单剂量ｐｏＣｙＡ胶囊后研究表明，其药时曲线符合一级吸收的双室模型。血药浓度约在１．２ｈ达到峰值８７９．９ｎｇ·ｍｌ－１，消除半衰期约为５ｈ。结论：本方法简便，准确，能较好地满足ＣｙＡ临床常规血药浓度监测及人体药动学过程研究。
OBJECTIVE: To establish a single-step extraction-RP-HPLC method for the determination of cyclosporine A (CyA) in human whole blood and study its pharmacokinetics and bioavailability in human. Methods: The blood samples were extracted with diethyl ether and the mobile phase was acetonitrile-methanol-water-isopropanol (57:18:25:1.5) Chromatography. Cyclosporine D was used as an internal standard and quantified by UV at 208 nm. The data obtained by PKBP N1 pharmacokinetic program fitting calculation, find the pharmacokinetic parameters. Results: The concentration of CyA in the range of 40 ~ 1200ng · ml-1 showed a good linear relationship with the peak area ratio of chromatin, the lowest detection concentration of CyA in whole blood was 20ng · ml-1, intra-day (n = 7) n = 6) RSD was 4.8% and 7.8%, the recovery rate was 98.6% ~ 99.5%. A single dose of 10 poCyA capsules in 10 normal young men showed that the pharmacokinetic profile conformed to the one-compartment dual-compartment model. The plasma concentration reaches a peak of 879.9 ng · ml-1 at about 1.2 h, and the elimination half-life is about 5 h. Conclusion: The method is simple and accurate, and can well meet the clinical routine blood concentration monitoring and pharmacokinetic study of CyA.