石墨炉原子吸收法用于奥沙利铂脂质体大鼠的药动学

A graphite furnace atomic absorption spectrometry for pharmacokinetic study of oxaliplatin liposome in rats

目的建立一种石墨炉原子吸收分析方法测定奥沙利铂脂质体大鼠静脉注射给药后的血药浓度,并考察其药动学行为。方法采用微波消解法对血浆样品进行前处理,使用石墨炉原子吸收光谱仪对药物浓度进行测定。大鼠分别尾静脉注射给药8 mg·kg-1的奥沙利铂脂质体和注射剂,不同时间取血,分离获得血浆样品,利用所建立的方法测定血浆中奥沙利铂的浓度,计算药动学参数,考察其药动学行为。结果本方法可以准确、精密测定大鼠血浆中奥沙利铂的药物浓度,线性为0.52~187.25 mg·L-1,日内和日间变异系数均小于15%,最低定量限为0.327 mg·L-1。奥沙利铂脂质体主要药动学参数:ρmax为(120.64±18.42)mg·L-1,t1/2为(11.61±5.22)h,V为(396.56±228.54)mL·kg-1,Cl为(24.07±9.43)mL·h-1·kg-1,AUC0-24为(311.38±93.29)mg·L-1·h。结论该方法可以用于奥沙利铂脂质体大鼠药动学的研究,满足体内分析方法要求。与市售注射剂相比,奥沙利铂脂质体最大血药浓度与药时曲线下面积均显著提高,消除半衰期延长,显著改善了对应注射剂的体内药动学行为。

Objective To establish a graphite furnace atomic absorption spectrometry for determination of oxaliplatin(OXP)in rat plasma after parenteral administration,and to research on pharmacokinetics.Methods Plasma sample was pretreated with microwave digestion.Then the concentration of drug was measured by graphite furnace atomic absorption spectrometry.Rats were injected intravenously with OXP-L or OXP-G at 8 mg·kg-1,and the plasma sample was separated after centrifugation.Ultimately,the concentration of drug was measured with the established method for pharmacokinetic parameters calculation,meanwhile the pharmacokinetics was studied.Results The method was proved to be accurate and precise for the measurement of OXP in rat plasma.It was linear between 0.52 and 187.25 mg·L-1,and its lower limit of quantification was 0.327 mg·L-1.The variation coefficients both intra-day and inter-day were less than 15%.The main pharmacokinetic parameters were calculated:ρmax=(120.64±18.42)mg·L-1,t1/2=(11.61±5.22)h,V=(396.56±228.54)mL·kg-1,Cl=(24.07±9.43)mL·h-1·kg,AUC0-24=(311.38±93.29)mg·L-1·h.Conclusion The method is able to meet the demands of pharmaceutical analysis in biological samples so that it could be used in pharmacokinetic study of oxaliplatin liposome.Compared with the commercially available OXP-G,theρmax and AUC0-t of OXP-L are improved significantly,and t1/2 of OXP-L is extended.The in vivo pharmacokinetic behavior of OXP-L is significantly improved.