肌注苯环壬酯在大鼠体内的药物动力学研究

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:t1/2α0.679 h,t1/2β3.98 h,t1/2Ka0.013h,tmax0.076 h,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。

Determination and Pharmacokinetics of Phencynonate in Rat

Objective Quantification and pharmacokinetics of phencynonate were investigated in rat by the method of high-performance liquid chromatographic assay with electro spray ionization mass spectrometry detection(LC-ESI-MS).Methods The chromatography was on BetaBasic-18 column(150mm×2.1mm 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 two-compartments open model after a single dose phencynonate(0.35mg/kg) intramuscularly.The main pharmacokinetic parameters of phencynonate were as follows:t_1/2α 0.679h,t_1/2β 3.98h,t_1/2Ka 0.013h,t_max 0.076h,C_max 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.