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

摘要/Abstract

摘要： 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310 nm，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8 mg，考察其药代动力学与生物利用度。结果定量限为0.25 ng·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±50 ng·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、30 ng·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T1/2分别为230.2±78.0 ng·h·mL^-1、265.2±101.5 ng·h·mL^-1，35.67±8.94 ng·mL^-1、1.51±0.79 h、5.00±1.41 h。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: 昂丹司琼, 昂丹司琼, 昂丹司琼, 高效液相色谱法, 高效液相色谱法, 高效液相色谱法, 口崩片, 口崩片, 口崩片, 药代动力学, 药代动力学, 药代动力学

Abstract: Aim 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 nm 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 ondansetron and about 90% for internal standard. Linearity was good within the concentration range of 0.5-50 ng·mL^-1 with r² 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%, and 99.51%±2.34%, respectively. Pharmacokinetic parameters of AUC0-t, AUC0-∞, Cmax, Tmax, and T1/2 were 230.2±78.0 ng·h·mL^-1, 265.2±101.5 ng·h·mL^-1, 35.67±8.94 ng·mL^-1, 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.

Key words: ondansetron, ondansetron, HPLC, HPLC, orally disintegrating tablets, orally disintegrating tablets, pharmacokinetics, pharmacokinetics

中图分类号:

R917.4

R945.1

Supporting: ^*Corresponding author. Tel.: 86-21-54237833

陈伟, 吴伟^*, 汪杨, 黄敏, 阙俐, 胡弢, 孙宁云. 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[J]. .

CHEN Wei, WU Wei^*, WANG Yang, HUANG Min, QUE Li, HU Tao, SUN Ning-yun. High Resolution Determination of Ondansetron in Human Plasma by HPLC and Pharmacokinetics of Orally Disintegrating Tablets[J]. .

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