摘要
目的:建立 SPE—HPLC 法测定人血浆中喹那普利及其代谢产物喹那普利拉的浓度,以研究喹那普利及喹那普利拉在健康志愿者中的药代动力学和相对生物利用度。方法:应用 C_(18)固相萃取柱提取血浆中喹那普利及喹那普利拉,喹那普利色谱条件为:迪马 Diamonsil C_(18)柱(150 mm×4.6 mm,5μm);流动相为乙腈-0.1%醋酸溶液(40:60,v/v);流速1.0 mL·min^(-1)。喹那普利拉色谱条件为:Phenomenex C_(18)柱(150 mm×4.6 mm,5μm);流动相为乙腈-0.005 mol·L^(-1)十二烷基磺酸钠(磷酸调 pH 2.5)(40:60,v/v);流速1.0 mL·min^(-1)。人体药代动力学试验采用单剂双周期交叉设计方案,将18名志愿者随机分为两组,分别口服参比制剂喹那普利片和试验制剂喹那普利胶囊各40 mg,清洗期为1周。结果:喹那普利的线性范围为10～800ng·mL^(-1),r=0.9931,最低定量限为10 ng·mL^(-1);提取回收率与方法回收率分别为82.1%～94.4%,92.6%～99.9%;日内、日间 RSD 均小于10%。喹那普利拉的线性范围为20～1200 ng·mL^(-1),r=0.9995,最低定量限为20 ng·mL^(-1);提取回收率与方法回收率分别为73.3%～94.0%,100.0%～105.9%;日内、日间 RSD 均小于7%。结论:本方法灵敏度高、特异性强、重复性好,测定结果可靠,统计学分析表明2种制剂的主要药代动力学参数无显著性差异,为等效制剂。
Objective ： To establish a SPE-HPLC method for the determination of quinapril and its active metabo-lite quinaprilat in human plasma and to evaluate their pharmacokinetics and relative bioavailability. Methods： Quinapril and quinaprilat in plasma were processed by CIS extraction column,and determined by methods as follows ：a C18 column（ Diamonsil, 150 mm × 4.6 mm ,5 μm）was used with a mobile phase of a mixture of acetonitrile- 0. 1% acetic acid（40： 60,v/v）at a flow rate of 1.0 mL · min^-1 for quinapril,and a CIS column（ Phenomenex,150 mm × 4. 6 mm,5 μm） was used with a mobile phase of a mixture of acetonitrile-sodium dodecylsulphate （0. 005 mol·L^-1 adjusted to pH 2. 5 with H3PO4） （40：60 ,v/v）at a flow rate of 1.0 mL·min^-1 for quinaprilat. To study the pharmacokinetics and relative bioavailability, a single dosage of 40 mg of reference quinapril tablets or test quinapril capsules was given to each 18 healthy male volunteers according to a randomized 2 -way cross-over design with 1 week washout period. Results：Quinapril：The linear range of the calibration curve was 10 -800 ng·mL^-1 with r=0.9931, and the determination limit was 10 ng ·mL^-1. The extraction recovery was 82. 1% - 94.4% while the method recovery was 92. 6% - 99. 9%. The intra-day and inter-day RSD were less than 10%. Quinaprilat ：The linear range of the calibration curve was 20-1200 ng·mL^-1 with r=0. 9995 ,and the determina-tion limit was 20 ng·mL^-1. The extraction recovery was 73.3% -94.0% while the method recovery was 100. 0% -105.9%. The intra-day and inter-day RSD were less than 7%. Conclusions： The results determined by the established SPE-HPLC method which is sensitive, specific and reproducible are reliable. No significant difference exists among the main pharmacokinetic parameters between the reference quinapril tablets and test quinapril capsules,which means that they are bioequivalence.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2008年第4期511-515,共5页
Chinese Journal of Pharmaceutical Analysis
