摘要
目的建立超高效液相色谱串联质谱法测定大鼠各组织中(R/S)-2-(2-羟基丙酰氨基)-5-三氟甲基苯甲酸[(R/S)-2-(2-hydroxypropanamido)-5-trifluoromethylbenzoic acid,R-/S-HFBA]浓度的方法,研究并比较(R/S)-HFBA在大鼠体内的组织分布特征。方法SD大鼠单次灌胃给药后分别于0.5、3、8 h采取心、肝、脾、肺、肾、胃、小肠、胸腺、肌肉、脂肪等脏器或组织,采用UPLC-MS/MS法测定各组织中HFBA的浓度。结果大鼠单次灌胃给药后0.5 h即可在各组织中检测到HFBA。R-HFBA在各组织中浓度排列顺序为:小肠>胃>肾>肺>心>肝>脂肪>脾>胸腺>肌肉;S-HFBA在各组织中浓度排列顺序为:小肠>胃>肾>肝>肺>心>脾>脂肪>胸腺>肌肉。结论R/S-HFBA在大鼠体内分布广泛且迅速,R-HFBA与S-HFBA在肝脏、肾脏的浓度具有显著差异,推测是由于两者存在立体选择性差异。R/S-HFBA比2-(2-羟基丙酰氨基)-苯甲酸[2-(2-hydroxypropanamido)benzoic acid,HPABA]在大鼠体内保留的时间更长,三氟甲基的引入提高了HFBA的代谢稳定性。
Objective To develop a method for the determination of R/S-2-(2-hydroxypropanamido)-5-trifluoromethylbenzoic acid(R/S-HFBA)in rat tissues by ultra-high performance liquid chromatography-tandem mass spectrometry,and to study and compare the tissue distribution characteristics of R/S-HFBA in rats.Methods The heart,liver,spleen,lung,kidney,stomach,small intestine,thymus,muscle,fat of SD rats were taken at 0.5 h,3 h and 8 h after a single intragastric administration,and the content of HFBA in tissues was determined by UPLC-MS/MS.Results HFBA could be detected in all tissues at 0.5 h after a single intragastric administration.The sequence of R-HFBA concentration in various tissues was as follows:small intestine>stomach>kidney>lung>heart>liver>fat>spleen>thymus>muscle.The sequence of S-HFBA concentration in various tissues was as follows:small intestine>stomach>kidney>liver>lung>heart>spleen>fat>thymus>muscle.Conclusion R/S-HFBA are distributed widely and rapidly in rats.There is a significant difference in the concentration of R-HFBA and S-HFBA in liver and kidney,which is presumed to be due to the difference of stereoselectivity between them.The retention time of R/S-HFBA in rats is longer than that of HPABA,and the introduction of trifluoromethyl improves the metabolic stability of HFBA.
作者
高若芳
刘露露
何丽娟
于治国
赵云丽
龙猜
GAO Ruofang;LIU Lulu;HE Lijuan;YU Zhiguo;ZHAO Yunli;LONG Cai(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)
出处
《沈阳药科大学学报》
2026年第1期87-93,100,共8页
Journal of Shenyang Pharmaceutical University
