目的 建立HPLC法測(cè)定大鼠血漿中泮托拉唑鈉對(duì)映體，研究泮托拉唑鈉在大鼠體內(nèi)藥動(dòng)學(xué)特征。方法 血漿用醋酸乙酯提取，以非那西丁為內(nèi)標(biāo)，Chiralcel OJ-RH色譜柱（250 mm×4.6 mm，5 μm），流動(dòng)相為20 mmol/L磷酸二氫鈉（含0.01%磷酸）-乙腈（78∶22），紫外檢測(cè)波長(zhǎng)為288 nm，體積流量為1.0 mL/min，柱溫40℃。大鼠尾iv消旋體16 mg/kg，HPLC-UV法測(cè)定血漿中左旋和右旋泮托拉唑鈉濃度，并采用DAS 2.0軟件計(jì)算藥動(dòng)學(xué)參數(shù)。結(jié)果 左旋泮托拉唑鈉、右旋泮托拉唑鈉線性范圍均為0.156～40.000 μg/mL，定量限為0.156 μg/mL。泮托拉唑鈉左旋體與右旋體的主要藥動(dòng)學(xué)參數(shù)分別為：C_max（38.13±3.33）、（40.52±3.69）μg/L；AUC_0-τ（1 688.45±302.38）、（1 399.88±376.44）min·μg/mL；AUC_0-∞（1710.61±309.40）、（1 417.29±383.21）min·μg/mL；t_1/2（30.92±6.41）、（22.37±7.59）h。結(jié)論 泮托拉唑鈉對(duì)映體在大鼠體內(nèi)的藥動(dòng)學(xué)存在立體選擇性特征，為臨床合理應(yīng)用手性藥物泮托拉唑鈉提供參考。

Objective To establish an HPLC method to determine pantoprazole sodium enantiomers in plasma, and study its pharmacokinetics in rats. Methods Pantoprazole sodium and phenacetin internal standard were extracted by liquid-liquid extraction and separated on Chiralcel OJ-RH column (250 mm×4.6 mm, 5 μm), with 20 mmol/L natrium biphosphoricum (containing 0.01% phosphoric acid)-acetonitrile (22:78) as mobile phase. The column temperature was set at 40℃, and the analytical wavelength was 288 nm with flow rate as 1.0 mL/min. Rats were tail iv administered with racemic pantoprazole sodium 16 mg/kg, and L- and D-pantoprazole sodium in plasma were determined by HPLC-UV method. DAS 2.0 software was used to calculate the pharmacokinetic parameters. Results The calibration curve was linear over the concentration range of 0.156-40.00 μg/mL with a sensitivity of 0.156 μg/mL as the limit of quantification. Main pharmacokinetic parameters were as following:C_max for L- and D-pantoprazole sodium were (38.13±3.33) and (40.52±3.69) μg/L; AUC_0-τ were (1 688.45±302.38) and (1 399.88±376.44) min·μg/mL; AUC_0-∞ were (1 710.61±309.40) and (1 417.29±383.21) min·μg/mL; t_1/2 were (30.92±6.41) and (22.37±7.59) min. Conclusion Pharmacokineties of pantoprazole enantiomers has a stereoseleetive character in rats, which provide reference for clinical rational application of chiral drug pantoprazole sodium.

中華醫(yī)學(xué)會(huì)醫(yī)學(xué)教育研究課題資助項(xiàng)目（2012-SY-44）