目的 建立HPLC-MS/MS法以測(cè)定大鼠血漿中鹽酸維拉帕米的血藥濃度，并考察其藥動(dòng)學(xué)特征。方法 采用ZORBAX Eclipse Plus C₁₈色譜柱（100 mm×2.1 mm，3.5 μm），流動(dòng)相為A相0.1%甲酸水，B相乙腈，梯度洗脫；體積流量為0.3 mL/min，柱溫為30℃，進(jìn)樣量為5 μL。離子源為電噴霧離子源（ESI），以多反應(yīng)離子監(jiān)測(cè)（MRM）進(jìn)行正離子檢測(cè)。鹽酸維拉帕米監(jiān)測(cè)離子對(duì)為m/z 455.3→m/z 165.0，內(nèi)標(biāo)地西泮監(jiān)測(cè)離子對(duì)為m/z 285.0→m/z 154.1。6只SD大鼠在ig鹽酸維拉帕米33.33 mg/kg后，對(duì)其進(jìn)行藥動(dòng)學(xué)的研究。結(jié)果 鹽酸維拉帕米在5~2 000 ng/mL顯示線性關(guān)系良好；日內(nèi)日間精密度（RSD）為1.3%~2.0%，準(zhǔn)確度（RE）范圍為0.1%~18.0%；提取回收率是90.87%~92.42%，基質(zhì)效應(yīng)為82.82%~101.99%。鹽酸維拉帕米在大鼠體內(nèi)主要藥動(dòng)學(xué)參數(shù)C_max、t_max、t_1/2、Ke、AUC_（0-tn）和AUC_（0-∞）分別為（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。結(jié)論 該方法靈敏度高、專屬性強(qiáng)，適用于測(cè)定大鼠血漿中鹽酸維拉帕米的血藥濃度及其藥動(dòng)學(xué)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.

國(guó)家自然科學(xué)基金資助項(xiàng)目（81673824）