手性固定相HPLC法测定人血浆中奥拉西坦2种异构体的浓度  

A chiral stationary phase HPLC method for oxiracetam enantiomers determination in Chinese healthy volunteers plasma

作　　者：梁大虎[1] 孙华[2] 袁小龙[1] 高春梅[1] 贾元威[2] 戴敏[2] 李相鸿[2] 周理想[2] 杨斌[2] 王伟佳[2] 谢海棠[2] 

机构地区：[1]皖南医学院,芜湖241002 [2]皖南医学院弋矶山医院临床药学部,芜湖241000

出　　处：《药物分析杂志》2016年第5期776-782,共7页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金面上项目(No 81173134);国家自然科学基金(81503236);安徽省科技厅自然科学基金项目(1608085QH212;1408085MH163);安徽高校自然科学研究重点项目(KJ2015A155)

摘　　要：目的:建立简便、快速、可靠的测定人血浆中S-奥拉西坦和R-奥拉西坦2种异构体浓度的HPLC测定方法,并用于2种异构体在人体内的药代动力学对比研究。方法:采用大赛璐CHIRALPAK ID(4.6 mm×250 mm,5μm)色谱柱,以异丙醇-无水乙醇-三氟乙酸(82∶18∶0.1)为流动相,流速1.2 m L·min-1,紫外检测波长为210 nm,柱温35℃,内标物为吡拉西坦。12名中国健康志愿者(男女各半)根据体重随机分组,采用双周期、双交叉给药设计。结果:2种异构体血浆药物浓度测定无内源性干扰,最低定量限为5.000 mg·L^(-1)。S-奥拉西坦与R-奥拉西坦质量浓度在5.000～400.0 mg·L^(-1)范围内线性关系均良好,相关系数分别为0.998 2和0.998 7。日内、日间精密度的RSD分别为1.6%～7.9%和2.3%～8.9%。准确度分别在94.0%～103.1%和91.0%～103.2%范围内。药动学结果显示,健康志愿者静脉滴注3.0 g S-奥拉西坦后S-奥拉西坦在人体内平均Cmax为(172.9±31.09)mg·L^(-1),平均t1/2为(2.22±0.42)h,平均AUC0-∞为(364.0±55.45)mg·L^(-1)·h;健康志愿者静脉滴注6.0 g消旋奥拉西坦后S-奥拉西坦与R-奥拉西坦在人体内平均Cmax分别为(183.8±37.13)mg·L^(-1)和(180.3±37.65)mg·L^(-1),平均t_(1/2)分别为(2.24±0.44)h和(2.34±0.47)h,平均AUC_(0-∞)分别为(386.7±70.61)mg·L^(-1)·h和(389.3±74.41)mg·L^(-1)·h。结论:经方法学验证,所建立的HPLC手性固定相法可应用于奥拉西坦两异构体在中国健康志愿者体内的药代动力学对比研究。Objective：To establish a simple,rapid and credible chiral stationary phase HPLC method for the determination of S-oxiracetam and R-oxiracetam in human plasma,so as to compare the pharmacokinetic difference of two enantiomers of oxiraceram in human after intravenous injection of S-oxiracetam and racemate oxiracetam,respectively.Methods：The study was perfermed on a CHIRALPAK ID（4.6 mm×250 mm,5 μm）column at 35℃ with the mobile phase of isopropanol-ethanol-trifluoroacetic acid（82∶18∶0.1）at a flow of 1.2 m L·min（-1）.The detection wavelength was set at 210 nm,and the internal standard substance was piracetam.The 12 Chinese healthy volunteers were divided into two groups randomly by gender and weight.The way of drug administration was designed in a two-period and double-cross pattern.Results：There was no endogenous interference in the determination of the oxiracetam enantiomers,and the low limit of quantification was 5.000 mg·L（-1） for both enantiomers.The calibration curves of both enantiomers were linear in the range of 5.000-400.0 mg·L（-1）,with the correlation coefficients of 0.998 2 and 0.998 7 for S-oxiracetam and R-oxiracetam,respectively.The relative standard deviation for intra-and inter-day precision were 1.6%-7.9% and 2.3%-8.9% for S-oxiracetam and R-oxiracetam,respectively.The accuracy ranged from 94.0% to 103.1% for S-oxiracetam and 91.0% to 103.2% for R-oxiracetam.In those healthy volunteers receiving intravenous injection of single 3.0 g S-oxiracetam,the mean Cmax was（172.9±31.09）mg·L（-1）,the meant _（1/2） was（2.22±0.42）h,and the mean AUC0- ∞was（364.0±55.45）mg·L（-1）·h.In healthy volunteers receiving intravenous injection of single 6.0 gracemate oxiracetam,the mean Cmax were（183.8±37.13）and（180.3±37.65）mg·L（-1）,the mean t1/2 were（2.24±0.44）and（2.34±0.47）h,and the mean AUC_（0-∞） were（386.7±70.61）and（389.3±74.41）mg·L（-1）·h for S-oxiracetam and R-oxiracetam,respectively.Conclusion：The establishe

关 键 词：S-奥拉西坦 R-奥拉西坦 异构体 人血药浓度 高效液相色谱 手性固定相 

分 类 号：R917[医药卫生—药物分析学]