High Resolution Determination of Ondansetron in Human Plasma by HPLC and Pharmacokinetics of Orally Disintegrating Tablets  

高灵敏度HPLC法测定血浆中昂丹司琼含量及口崩片的生物利用度(英文)

作　　者：陈伟[1] 吴伟[2] 汪杨[2] 黄敏[2] 阙俐[2] 胡弢[2] 孙宁云[2] 

机构地区：[1]上海市药品和医疗器械审评中心,上海200021 [2]复旦大学药学院,上海200032

出　　处：《Journal of Chinese Pharmaceutical Sciences》2005年第3期162-168,共7页中国药学（英文版）

摘　　要：Ahn To develop a high resolution HPLC method for the determination of ondansetron in human plasma and to study the pharmacokinetics of ondansetron in orally disintegrating tablets. Methods HPLC determination involved liquid-liquid extraction, separation on a CN column and ultraviolet detection at 310 ran with granisetron as an internal standard. Pharmacokinetics and bioequivalence of ondansetron in orally disintegrating tablets by direct compression and conventional 8 mg tablets were evaluated and compared in 20 healthy human male volunteers after a single oral dose in a randomized cross-over study. Results The limit of quantification was 0.25 ng· mL^-1. The recovery was about 85 % or over for ondan setron and about 90% for internal standard. Linearity was good within the concentration range of 0.5 - 50 ng·mL^-1 with r^2 ranging from 0.997 1 to 0.999 9. Intra- and inter-assay coefficients of variation ranged from 1.78% to 2.38% and 3.88% -5.19%, respectively. Accuracies for spiked concentrations of 2.0, 10.0, and 30.0 ng·mL^-1 were 104.7% ±4.4%, 102.2% ± 1.1%, and99.51% ±2.34%, respectively. Pharmacokinetic parameters of AUCo-t, AUCo-∞ , Cmax, Tmax, and T1/2 were 230.2 ± 78.0 ng·h·L^-1 , 265.2± 101.5 ng·h·mL^-1, 35.67 ± 8.94 ng·mL^-l, 1.51 ±0.79 h, and 5.00± 1.41 h for orally disintegrating tablets, respectively. The analysis of variance did not show any significant difference between orally disintegrating tablets and conventional tablets, and 90% confidence intervals fell within the acceptable range for bioequivalence. Conclusion High resolution HPLC method has been set up and applied in pharmacokinetic evaluation of ondansetron in orally disintegrating tablets.目的建立高灵敏度HPLC法测定血浆中昂丹司琼含量,并研究盐酸昂丹司琼口崩片的生物利用度。方法采用液—液萃取,氰基柱分离,检测波长为310nm,格拉司琼为内标。随机交叉设计,20名健康志愿者单剂量口服盐酸昂丹司琼口崩片或普通片8mg,考察其药代动力学与生物利用度。结果定量限为0.25ng·mL-1,昂丹司琼和内标的提取回收率约为85%和90%,线性范围为0.5±50ng·mL-1,相关系数介于0.9971-0.9999。批内与批间精密度分别介于1.78%～2.38%和3.88%～5.19%。浓度分别为2、10、30ng·mL-1的质控样品的回收率分别为104.7%±4.4%、102.2%±1.1%、99.51%±2.34%。口崩片的AUC0-t、AUC0-∞、Cmax、Tmax和T12分别为230.2±78.0ng·h·mL-1、265.2±101.5ng·h·mL-1,35.67±8.94ng·mL-1、1.51±0.79h、5.00±1.41h。方差分析表明口崩片和普通片的药动学参数无显著性差异,90%可信限介于生物等效范围之内。结论建立了高灵敏度HPLC法测定昂丹司琼的含量,并应用于盐酸昂丹司琼口崩片药动学和生物利用度评价。

关 键 词：ONDANSETRON HPLC orally disintegrating tablets PHARMACOKINETICS 

分 类 号：R96[医药卫生—药理学]