液-质联用法测定大鼠血浆中索他洛尔的浓度及其药动学研究

目的：建立大鼠血浆中索他洛尔的LC-MS/MS定量分析方法，考察口服给药后，索他洛尔在大鼠体内的药动学特征。方法：大鼠口服给药，分别在给药前和给药后不同的时间点从眼底静脉丛取血。采用LC-MS/MS分析方法，以阿替洛尔为内标测定大鼠血浆中索他洛尔的含量，并运用DAS1.0软件计算待测药物各药动学参数。结果：索他洛尔在5~5 000 ng·mL^-1范围内线性关系良好；日内日间精密度（RSD）范围为2.99%~5.75%，准确度（RE）为98.56~105.71%；提取回收率为92.50%~97.16%，基质效应为96.59%~102.10%。结论：所建立的LC-MS/MS分析方法准确、灵敏，可用于大鼠血浆中的索他洛尔的含量测定和药动学研究。

Determination of sotalol in rat plasma by HPLC-MS/MS method and its application in pharmacokinetic study

OBJECTIVE To establish a sensitive and reliable LC-MS/MS method to study the pharmacokinetic characteristics of sotalol in rats after oral administration.METHODS Blood samples were obtained from the fossa orbitalis at different times. LC-MS/MS method was developed and validated for the determination of sotalol in rats using atenolol as the internal standard. The pharmacokinetic parameters were acquired by employing DAS 1.0 software.RESULTS Calibration curves were linear in range of 5-5 000 ng·mL^-1 for sotalol. Intra-and Inter-day precision and accuracy were 2.99%-5.75% and 98.56%-105.71%, respectively. Extraction recovery ranged 92.50%-97.16%, and the matrix effect of sotalol ranged 96.59%-102.10%.CONCLUSION The LC-MS/MS method is accurate and sensitive, and is successfully applied to evaluate the pharmacokinetics of sotalol in rats.