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目的:建立口服复方替米沙坦片后氢氯噻嗪血药浓度的液相色谱-质谱(LC-MS/MS)测定法,进行人体药动学研究。方法:20例健康受试者随机分成两组,分别口服低剂量(1片)和高剂量(2片)受试制剂复方替米沙坦片(每片含替米沙坦40 mg,氢氯噻嗪12.5 mg),应用LC-MS/MS法测定样品中氢氯噻嗪的血药浓度。结果:口服低剂量和高剂量受试制剂(分别含氢氯噻嗪12.5 mg和25 mg)后,估算的氢氯噻嗪的药动学参数C_(max)分别为(78±15)μg·L~(-1),(150±50)μg·L~(-1);t_(max)分别为(1.9±0.7)h,(2.4±0.9)h;AUC_(0-1)分别为(591±163)μg·h·L~(-1),(1026±306)μg·h·L~(-1);AUC_(0-∞)分别为(601±157)μg·h·L~(-1),(1039±303)μg·h·L~(-1);t_(1/2)分别为(7.1±±1.5)h,(9.3±2.9)h;CLz/F分别为(22.1±5.6)L·h~(-1),(25.8±6.6)L·h~(-1);Vz/F分别为(226±77)L,(341±130)L;MRT分别为(8.4±1.3)h,(8.7±1.9)h。结论:本方法结果准确,灵敏度高,氢氯噻嗪进入人体分布后,其主要药动学参数与文献报道单方氢氯噻嗪数据一致。
Objective: To establish a liquid chromatography-mass spectrometry (LC-MS / MS) method for the determination of hydrochlorothiazide after oral administration of telmisartan tablets. Methods: Twenty healthy subjects were randomly divided into two groups: oral low dose (1 tablet) and high dose (2 tablet) of test compound telmisartan tablets (each containing telmisartan 40 mg, hydrochlorothiazide 12.5 mg), the plasma concentration of hydrochlorothiazide in the sample was determined by LC-MS / MS. RESULTS: The estimated pharmacokinetic parameters Cmax of hydrochlorothiazide were (78 ± 15) μg · L -1 after oral administration of low dose and high dose of test compound (hydrochlorothiazide 12.5 and 25 mg, respectively) , (150 ± 50) μg · L -1; t max was (1.9 ± 0.7) h and (2.4 ± 0.9) h respectively; AUC 0-1 was 591 ± 163 μg · (-1), (1026 ± 306) μg · h · L -1 and AUC 0 -∞ were (601 ± 157) μg · h · L -1, ( The mean value of CLz / F were (22.1 ± 5.6) L · (-1) and h, and 25.8 ± 6.6 L · h -1, Vz / F were (226 ± 77) L and (341 ± 130) L, respectively; MRT was (8.4 ± 1.3) (8.7 ± 1.9) h. Conclusion: The method is accurate and sensitive. The main pharmacokinetic parameters of hydrochlorothiazide are consistent with those reported in the literature.