摘要
目的:建立LC-MS测定人血浆中尼索地平浓度的方法,测定志愿者口服尼索地平胶囊后的血药浓度,并对试验制剂与参比制剂的生物等效性进行评价。方法:血浆中加入内标尼莫地平,碱化后经乙酸乙酯提取,进行LC-MS测定。色谱柱为Agilent ODS C18(5μm,250 mm×4.6 mm),流动相为甲醇-水(80:20),流速为1.0 mL·min-1;ESI选择性正离子检测。临床实验方案采用双交差实验设计。结果:尼索地平血浆线性范围为0.5-20 ng·mL-1,检测限为0.2 ng·mL-1,定量限为0.5ng·mL-1,方法回收率大于85%。测定了20名志愿者单剂量交叉口服试验制剂与参比制剂后的血药浓度经时过程,二者的主要药代动力学参数无显著性差异,试验制剂的相对生物利用度为(100.7±15.9)%。结论:本方法专属性强,灵敏度高,准确性好。试验制剂与参比制剂生物等效。
Objective:To establish a LC-MS method for study of bioavailability and pharmacokinetics of nisoldipine in human plasma. Methods: After adding nimodipine, the internal standard, and 0.5 mL of 1 mol·L-1 NaOH sulution,the plasma samples were extracted with ethyl acetate and determined by LC-MS. The mobile phase was CH3 OH-H2O(80:20,). Analysis were run at flow rate of 1.0 mL·min -1. Concentrations of nisoldipine in plasma of 20 male volunteers after oral administration of 20 mg nisoldipine test and reference capsules were determined, in random 2 - way cross - over design. Pharmacokinetic parameters were also estimated. Results: Nisoldipine exhibited a linear rang from 0. 5 to 20.0 ng·mL -1 with a correlation coefficient of 0. 9995. The limit of detection is 0.2 ng·mL-1. For the two team,Tmax were(2.5±0.4)h and(2. 4±0. 3)h,Cmax were (7.13±2. 17)ng·mL-1 and(7.02±1.95)ng·mL-1,AUC0-∞ were(39.97±14.61)h·ng·mL-1 and(40.27±15.82)h·ng·mL-1 ,T1/2 were (3. 80±0. 90)h and(3. 89±1. 21 )h,respectively. Conclusion:The test capsules were found to be bioequivalent to the reference capsules. The method is simple, sensitive and rapid.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2004年第2期126-129,共4页
Chinese Journal of Pharmaceutical Analysis
