肌注苯环壬酯在大鼠体内的药物动力学研究

Determination and Pharmacokinetics of Phencynonate in Rat

目的 研究苯环壬酯在大鼠血液中的高效液相色谱-电喷雾离子阱质谱测定方法及其药物动力学。方法 以BetaBasic-18色谱柱分离苯环壬酯，正离子电喷雾离子阱质谱法检测，内标法定量。结果 苯环壬酯在大鼠血中的线性范围为1～100μg／L，萃取回收率为69．6％～79．1％，日内与日间精密度均小于10％，最低定量限为1μg／L。单剂量肌肉注射（im）给药后，苯环壬酯在大鼠体内的血药时程符合一级吸收二室模型，其主要药物动力学参数为：t1／2α 0．679h，t1/2β 3．98h，t1／2Ka 0．013h，tmax0．076h，Cmax54．1μg／L，血药浓度-时间曲线下面积（AUC）77．7（ng·h）／mL。结论 该检测方法省时，重现性好，具有较高的灵敏度。药物动力学结果为开发新药与临床应用提供理论依据。

Objective Quantification and pharmacokinetics of phencynonate were investigated in rat by the method of highperformance liquid chromatographic assay with electro spray ionization mass spectrometry detection （LC-ESI-MS）. Methods The chromatography was on BetaBasic-18 column （150 mm× 2.1 mm id, 3μm）. Mass spectrometric measurements were performed on ion-trap mass spectrometer equipped with ESI source working in positive ion mode. Results The linearity was obtained over the concentration range of 1-100μg/L in rat blood. The lower limit of quantification was at 1μg/L in blood. Extraction recoveries were in the range of 69.6% - 79. 1%. The concentration-time curves in rats were all best fitted to first order absorption twocompartments open model after a single dose phencynonate （0.35 mg/kg） intramuscularly. The main pharmacokinetic parameters of phencynonate were as follows：t1/2α 0. 679 h, t1/2β 3.98 h, t1/2Ka 0. 013 h, tmax 0. 076 h, Cmax 54.1μg/L, AUC 77.7 （ng·h）/mL. Conclusion The method is simple, sensitive and specific. It is successfully applied for quantification of phencynonate and for the clinic drug monitoring and the pharmacokinetic studies.