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。
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 C18 column（150 mm× 4.6 mm,5μm）. The mobile phase was composed of methanol（A）-water（B） in gradient elution at a flow rate of 1 ml/min, 0-2 min A ： B：20 ： 80,2-7 min A ： B=95 ： 5,7-9 min A ： B=20 ： 80. Negative ion multiple reaction monitoring（MRM） of m/z 205→171（1ipoic acid） and m/z 205→161（internal standard ibuprofen） was detected. Pharmacokinetic parameters of lipoic acid were calculated after ga- vage 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. 005-5 μg/ml and the limit of quantity was 0. 005 μg/ml. The intra-day and inter-day RSD were 〈15%. The main phar- macokinetic parameters of the first and last administration were as follows： AUC0-24 h were （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 ,Cmax were （24.34±2.50） and （22.23± 2.61） 1g/ml,t~/2 were （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.
出处
《药学服务与研究》
CAS
2015年第4期265-268,共4页
Pharmaceutical Care and Research
关键词
硫辛酸
毒代动力学
色谱法
高效液相
串联质谱法
lipoic acid
toxicokinetics, chromatography, high performance liquid, tandem mass spectrometry
