测定人尿液中替米沙坦的LC-MS/MS方法及其应用

Determination of telmisartan in human urine by LC-MS/MS and its application

目的建立测定人尿液中替米沙坦的LC-MS/MS方法(液相色谱-串联质谱法),并应用于中国健康受试者口服替米沙坦后的尿液样本分析,以探究中国人群中替米沙坦的尿液排泄情况。方法尿液样本分别未经酶解及酶解处理后,采用液液萃取法提取后进样测定,未经酶解处理所得为尿液中替米沙坦原形,经酶解处理所得为尿液中替米沙坦总量,而两者之差即为以葡萄糖醛酸结合物形式存在的替米沙坦。结果替米沙坦尿药浓度在1.00～500.00ng/mL范围内线性关系良好,定量下限为1.00ng/mL;相对误差(RE)在±15%以内,批内相对标准偏差(RSD)、批间RSD均小于15%。中国健康受试者尿液中以替米沙坦葡萄糖醛酸结合物形式存在的替米沙坦占尿液总排泄量的98%左右,替米沙坦经由尿液排泄的数量不到给药剂量的1%。结论实验建立的LC-MS/MS方法专属准确、简单灵敏、分析速度快,可满足尿液未经酶解及酶解后替米沙坦测定的要求。中国人群的替米沙坦尿液排泄情况与西方人群并无差异。

Objective To establish LC-MS/MS method for the determination of telmisartan in human urine,analyze urine sam-ples collected from healthy Chinese volunteers,and study the urinary excretion of telmisartan in Chinese. Methods Urine samples were analyzed following incubation with glucuronidase or not, and then treated with a liquid-liquid extraction method, so the differ-ence of amount of telmisartan obtained by these two processing methods just was the amount of telmisartan which was present as telmisartan glucuronide. Results The calibration curve was linear over the concentration range of 1.00-500 ng/mL with the low-est detection limit of 1.00 ng/mL. Intra-batch and inter-batch RSD were both less than 15 %, and the RE were within ± 15 %. In Chinese healthy volunteers,about 98% of telmisartan in urine was present as telmisartan glucuronide,and urinary excretion accoun- ted for 〈1% of the dose. Conclusion The method is specific, sensitive and effective,and satisfy the determination of telmisartan in urine following incubation with glucuronidase or not. The urinary excretion of telmisartan in Chinese was similar to westerners.