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[摘要]
目的 建立HPLC法测定大鼠血浆中泮托拉唑钠对映体,研究泮托拉唑钠在大鼠体内药动学特征。方法 血浆用醋酸乙酯提取,以非那西丁为内标,Chiralcel OJ-RH色谱柱(250 mm×4.6 mm,5 μm),流动相为20 mmol/L磷酸二氢钠(含0.01%磷酸)-乙腈(78∶22),紫外检测波长为288 nm,体积流量为1.0 mL/min,柱温40℃。大鼠尾iv消旋体16 mg/kg,HPLC-UV法测定血浆中左旋和右旋泮托拉唑钠浓度,并采用DAS 2.0软件计算药动学参数。结果 左旋泮托拉唑钠、右旋泮托拉唑钠线性范围均为0.156~40.000 μg/mL,定量限为0.156 μg/mL。泮托拉唑钠左旋体与右旋体的主要药动学参数分别为:Cmax(38.13±3.33)、(40.52±3.69)μg/L;AUC0-τ(1 688.45±302.38)、(1 399.88±376.44)min·μg/mL;AUC0-∞(1710.61±309.40)、(1 417.29±383.21)min·μg/mL;t1/2(30.92±6.41)、(22.37±7.59)h。结论 泮托拉唑钠对映体在大鼠体内的药动学存在立体选择性特征,为临床合理应用手性药物泮托拉唑钠提供参考。
[Key word]
[Abstract]
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:Cmax for L- and D-pantoprazole sodium were (38.13±3.33) and (40.52±3.69) μg/L; AUC0-τ were (1 688.45±302.38) and (1 399.88±376.44) min·μg/mL; AUC0-∞ were (1 710.61±309.40) and (1 417.29±383.21) min·μg/mL; t1/2 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.
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[基金项目]
中华医学会医学教育研究课题资助项目(2012-SY-44)