泮托拉唑钠在大鼠体内药动学研究

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,5μm),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 m L/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0.156~40.000μg/m L,定量限为0.156μg/m L。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/m L;AUC0-∞(1710.61±309.40)、(1 417.29±383.21)min·μg/m L;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。

Pharmacokinetics of pantoprazole sodium in rats

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, 5μm), 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 weretail iv administered with racemic pantoprazole sodium 16 mg/kg, andL-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 — 40.00μg/mL with a sensitivity of 0.156μg/mL as the limit of quantification. Main pharmacokinetic parameters were as following:Cmax forL-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.