高效液相法测定大鼠血浆中阿苯达唑及其代谢产物阿苯达唑亚砜的含量

Determination of albendazole and its metabolite by HPLC in rats

目的：采用HPLC法建立快速测定大鼠血浆中阿苯达唑（ABZ）和阿苯达唑亚砜（ABZSX）的含量，为新制剂的处方筛选和药动学研究奠定基础。方法：在碱性条件下，用乙酸乙酯对血浆进行提取；采用高效液相色谱法，色谱柱为C18柱，流动相为甲醇-乙腈（1∶1），调节水相比例进行梯度洗脱，在0-28 min，水相比例由70%-30%，在28-30 min其比例由30%-70%；检测波长为292 nm；柱温为35℃；流速为1 mL.min^-1。结果：ABZ和ABZSX分别在0.025-1.992 mg.L-1和0.025-16.208 mg.L^-1呈良好的线性；平均提取回收率分别为96.94%和99.71%；准确度分别为100.42%和102.66%；ABZ和ABZSX日内和日间精密度RSD均〈8%。结论：此法可用于新制剂的药动学研究中。

Objective：To develop a rapid HPLC method for the simultaneous quantification of albendazole （ABZ） and its metabolite, albendazole sulphoxide （ABZSX）, in rat plasma. Methods： Plasma samples were extracted with ethyl acetate under alkaline conditions. Separation was achieved on a C18 reversed-phase analytical column at 35 % with UV detection at 292 nm. A gradient separation was applied according to the difference in the hydrophobicities of ABZ and its metabolites. The mobile phase consisted of a mixture of methanol-aeetonitrile （ 1 ： 1 ） and 0.05% formic acid. The proportion of organic modifier was increased from 30% to 70% in 28 min, then from 70% to 30% in 30 min. Mobile phase flow rate was 1.0 mL·min^-1. Results： The assay was linear for concentration ranges of 0. 025 -1. 992 mg·L^-1 for ABZ and 0. 025 - 16. 208 mg·L^-1 for ABZSX in rat plasma. The mean extraction recoveries of ABZ and ABZSX were 96.94% and 99.71% ; their mean recoveries were 100.42% and 102.66% , respectively. The within-day and day-to-day coefficients of variation of ABZ and ABZSX were less than 8%. Conclusion： The method developed in this study can be applied to determine the plasma levels of ABZSX and ABZ in pharmacokinetic studies.