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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。
OBJECTIVE To establish a high-sensitivity HPLC method for the determination of ondansetron in plasma and to study the bioavailability of ondansetron hydrochloride orally disintegrating tablets. Methods Liquid-liquid extraction and column separation were used. The detection wavelength was 310 nm and granisetron was the internal standard. Randomized crossover design, 20 healthy volunteers oral Oral Dan Occitane Orally disintegrating tablets or ordinary tablets 8mg, investigated its pharmacokinetics and bioavailability. Results The limit of quantification was 0.25 ng · mL-1. The recovery rates of ondansetron and internal standard were about 85% and 90%, respectively. The linear range was 0.5 ± 50 ng · mL-1 and the correlation coefficient was 0.9971-0.9999. Intra-batch and inter-batch precision were between 1.78% ~ 2.38% and 3.88% ~ 5.19%. The recoveries of the control samples with the concentrations of 2, 10 and 30 ng · mL-1 were 104.7% ± 4.4%, 102.2% ± 1.1% and 99.51% ± 2.34%, respectively. The AUC0-t, AUC0-∞, Cmax, Tmax and T12 of the orally disintegrating tablets were 230.2 ± 78.0 ng · h-mL-1,265.2 ± 101.5 ng · h-mL-1 and 35.67 ± 8.94 ng · mL- 1.51 ± 0.79h, 5.00 ± 1.41h. Analysis of variance showed no significant difference in pharmacokinetic parameters between orally disintegrating tablets and plain tablets, with 90% confidence limits lying within the bioequivalence range. Conclusion High sensitive HPLC method was established for the determination of ondansetron and its application in the evaluation of the pharmacokinetics and bioavailability of Ondansetron hydrochloride orally disintegrating tablets.