LC-MS/MS法测定氯沙坦及其代谢物的血浆浓度及氯沙坦钾片生物等效性评价  

Determination of losartan and its metabolite in human plasma by LC-MS/MS and bioequi valence study of losartan potassium tablets

作　　者：苑菲[1] 许剑安[1] 汪红[1] 储楠楠[1] 徐红蓉[1] 李雪宁[1] 陈伟力[1] 

机构地区：[1]复旦大学附属中山医院临床药理研究室,上海200032

出　　处：《中国临床药学杂志》2013年第1期13-18,共6页Chinese Journal of Clinical Pharmacy

摘　　要：目的建立LC-MS/MS法测定氯沙坦及其代谢物的血浆浓度,并在健康受试者口服氯沙坦钾片受试制剂及参比制剂后,评价其生物等效性。方法采用开放、随机、单剂量、2×2的交叉设计,24名健康中国男性受试者服用50mg氯沙坦钾片受试制剂或参比制剂后,在48 h内采集血浆样本,用LC-MS/MS测定血浆中氯沙坦及氯沙坦酸的浓度。每个洗脱周期至少为7 d。结果氯沙坦钾片受试制剂及参比制剂中氯沙坦的t_(max)分别为(1.42±0.99)和(1.50±1.14)h,P_(max)分别为(273.44±170.44)和(285.96±157.89)μg·L^(-1),AUC_(0→t)分别为(618.51±386.50)和(587.92±331.92)μg·h·L^(-1),相对生物利用度(F)为(105.87±26.07)%;其主要代谢产物氯沙坦酸的t_(max)分别为(3.69±1.16)和(3.96±1.30)h,ρ_(max)分别为(444.53±133.53)和(412.88+128.80)μg·L^(-1),AUC_(0→t)分别为(3 563.52±932.14)和(3 398.77±915.06)μg·h·L^(-1),F为(105.92±14.65)%。结论本法灵敏度高、专一性好,适用于氯沙坦的药动学研究以及测定需求。氯沙坦钾片受试制剂和参比制剂生物等效。AIM To build a LC-MS/MS method to evaluate bioavailability and bioequivalence of losartan and its metabolite after oral administration of test preparation and reference preparation of losartan potassium in healthy volun- teers. METHODS This was an open, randomized, single dose and 2 × 2 cross-over trial. A total of 24 Chinese healthy male subjects were given oral dose of 50 nag test or reference preparation losartan. Blood samples were collected up to 24 h after dosing. Plasma concentrations of losartan and losartan acid were determined by LC-MS/MS. RESULTS The tmax of losartan in test preparation and reference preparation were （ 1.42 ± 0.99） and （ 1.50 ± 1.14）h, ρmax were （273.44 ± 170.44） and （285.96± 157.89）μg· L- 1, AOC0→t were （618.51 ± 386.50） and （587.92± 331.92）p.g＇ h＂ L- I. Rela- tive bioavailability was （ 105.87 ± 26.07） % .The tmax of losartan acid in test preparation and reference preparation were （3.69±1. 16） and （3.96 ± 1.30）h,ρmax were （444.53 ± 133.53） and （412.88 ± 128.80）μg·L-1,AUC0→t were （3 563.52 ±932.14） and （3 398.77 ±915.06）μg· h· L-1. Relative bioavailability of losartan acid was （ 105.92 ±14.65）%. CONCLUSION The LC-MS/MS method is proved to be a sensitive and suitable for pharmacokinetie re- search and detemlinadon of losartan. The two preparations are bioequivalent.

关 键 词：氯沙坦 氯沙坦酸 LC-MS MS 生物等效性 

分 类 号：R96[医药卫生—药理学]