【摘要】 目的:建立测定SD大鼠血浆中硫辛酸的HPLC-MS/MS法,并将其应用于硫辛酸的毒代动力学研究。方法:采用XAqua C18色谱柱(150mm×4.6mm,5μm);流动相为甲醇(A)∶水(B),0~2min A∶B=20∶80,2~7min A∶B=95∶5,7~9min A∶B=20∶80,梯度洗脱9min;流速为1ml/min。采用负离子多反应监测模式(MRM)进行监测,离子对:硫辛酸m/z205→171,内标布洛芬m/z205→161,测定大鼠连续28d灌胃硫辛酸300mg/kg后的主要药动学参数。结果:硫辛酸线性范围为0.005~5μg/ml,最低定量限为0.005μg/ml;日内和日间精密度良好,RSD均<15%。大鼠初次和末次给药后的AUC0~24h分别为(23.16±2.45)和(21.27±2.62)μg·h·ml-1,AUC0~∞分别为(23.70±2.56)和(21.67±2.66)μg·h·ml-1,cmax分别为(24.34±2.50)和(22.23±2.61)μg/ml,t1/2分别为(5.22±0.57)和(4.96±0.23)h。硫辛酸在SD大鼠体内无明显的药物蓄积现象。结论:该方法灵敏度高、专属性强、操作简便,适用于生物样本中硫辛酸的测定及毒代动力学研究。更多还原

【Abstract】 Objective:To establish a HPLC-MS/MS method for concentration determination of lipoic acid in rat plasma and study its toxicokinetics.Methods:The analysis was performed on XAqua C18column(150mm×4.6mm,5μm).The mobile phase was composed of methanol(A)-water(B)in gradient elution at a flow rate of 1ml/min,0-2min A∶B=20∶80,2-7min A∶B=95∶5,7-9min A∶B=20∶80.Negative ion multiple reaction monitoring(MRM)of m/z 205→171(lipoic acid)and m/z205→161(internal standard ibuprofen)was detected.Pharmacokinetic parameters of lipoic acid were calculated after gavage of 300 mg/kg to the rats for 28 d.Results:The calibration curve of lipoic acid had a good linearity within the range of 0.005-5μg/ml and the limit of quantity was 0.005μg/ml.The intra-day and inter-day RSD were<15%.The main pharmacokinetic parameters of the first and last administration were as follows:AUC0-24hwere(23.16±2.45)and(21.27±2.62)μg·h·ml-1,AUC0-∞were(23.70±2.56)and(21.67±2.66)μg·h·ml-1,cmaxwere(24.34±2.50)and(22.23±2.61)μg/ml,t1/2were(5.22±0.57)and(4.96±0.23)h,respectively.There was no significant drug accumulation in SD rats.Conclusion:The method is sensitive,specific,convenient and suitable for the determination of lipoic acid in biological samples as well as toxicokinetic study.更多还原