目的 建立HPLC-MS/MS法以测定大鼠血浆中盐酸维拉帕米的血药浓度，并考察其药动学特征。方法 采用ZORBAX Eclipse Plus C₁₈色谱柱（100 mm×2.1 mm，3.5 μm），流动相为A相0.1%甲酸水，B相乙腈，梯度洗脱；体积流量为0.3 mL/min，柱温为30℃，进样量为5 μL。离子源为电喷雾离子源（ESI），以多反应离子监测（MRM）进行正离子检测。盐酸维拉帕米监测离子对为m/z 455.3→m/z 165.0，内标地西泮监测离子对为m/z 285.0→m/z 154.1。6只SD大鼠在ig盐酸维拉帕米33.33 mg/kg后，对其进行药动学的研究。结果 盐酸维拉帕米在5~2 000 ng/mL显示线性关系良好；日内日间精密度（RSD）为1.3%~2.0%，准确度（RE）范围为0.1%~18.0%；提取回收率是90.87%~92.42%，基质效应为82.82%~101.99%。盐酸维拉帕米在大鼠体内主要药动学参数C_max、t_max、t_1/2、Ke、AUC_（0-tn）和AUC_（0-∞）分别为（922.1±300.4）ng/mL、（0.54±0.25）h、（6.46±3.18）h、（0.13±0.05）1/h、（7 634.1±4 436.6）h· ng/mL和（10 548.1±8 024.8）h· ng/mL。结论 该方法灵敏度高、专属性强，适用于测定大鼠血浆中盐酸维拉帕米的血药浓度及其药动学研究。

Objective To establish a HPLC-MS/MS method for the determination of verapamil hydrochloride in rat plasma and to investigate its pharmacokinetics. Methods The determination was carried out on ZORBAX Eclipse Plus C₁₈ column (100 mm×2.1 mm, 3.5 μm), mobile phase was phase A 0.1% formic acid water, phase B acetonitrile with gradient elution, flow rate was 0.3 mL/min, column temperature was 30℃. The sample volume was 5 μL. The ion source was an electrospray ionization source (ESI) with positive ion detection using multiple reactive ion monitoring (MRM). The monitoring ion pair of verapamil hydrochloride was m/z 455.3→m/z 165.0, and the internal standard diazepam monitoring ion pair was m/z 285.0→m/z 154.1. Six SD rats were perfused with hydrochloric acid. Pharmacokinetic studies were performed after verapamil 33.33 mg/kg. Results The linear relationship of verapamil hydrochloride in the range of 5-2 000 ng/mL was good; intra-and inter-day precision and accuracy were 1.3%-2.0% and 0.1%-18.0%, respectively. The extraction recovery is 90.87%-92.42%, and the matrix effect is 82.82%-101.99%. The main pharmacokinetic parameters C_max, T_max, T_1/2, Ke, AUC_(0-tn) and AUC_(0-∞) of verapamil hydrochloride in rats were (922.1±300.4) ng/mL, (0.54±0.25) h, (6.46±3.18) h, (0.13±0.05) 1/h, (7 634.1±4 436.6) h·ng/mL and (10 548.1±8 024.8) h·ng/mL. Conclusion This method is sensitive and specific, and is suitable for the determination of plasma concentration and pharmacokinetics of verapamil hydrochloride in rat plasma.

国家自然科学基金资助项目（81673824）