Determination of compound lisinopril and hydrochlorothiazide tablets in human plasma with LC-MS method and application in pharmacokinetic study

AIM: To assess the effect of high protein and fat diet on the pharmacokinetic profiles of com- pound lisinopril and hydrochlorothiazide tablets (lisinopril, 10 mg; hydrochlorothiazide, 12.5 mg) by LC-MS. METHODS: The study was conducted according to an open, randomized, 2-period crossover design with a 1-week washout interval, which was administrated with a tablet of compound lisinopril and hydrochlorothiazide tablet on an empty stomach or after meal. The plasma concentrations of lisinopril and hydrochlorothiazide were measured by a fully validated LC-MS method. RESULTS: The major pharmacokinetic parameters of the single doses study on an empty stomach and after meal were as follows: for lisinopril-tmax were (7.3±s 1.2) vs (7.5±1.0) h; cmax were (42±7) vs (33±10)μg·L-1; t1/2 were (13.7±2.0) vs (12.5±2.2) h; MRT were (20±3) vs (19.9±2.5) h; AUC0-72 were (545±147) vs (493±125)μg·h·L-1, respectively. As for hydrochlorothiazide-tmax were (2.8±0.7) vs (4.6±1.1) h; cmax were (82±23) vs (77±13)μg·L-1; t1/2 were (8.6±1.8) vs (8.4±1.7) h; MRT were (10.4±2.0) vs (11.6±1.6) h; AUC0-48 were (680±281) vs (684±834)μg·h·L-1, respectively. CONCLUSION: LC-MS method is sensitive, convenient and proved to be suitable for clinical investigation of lisinopril and hydrochlorothiazide pharmacokinetics. High protein and fat diet could influence lisinopril's cmax and hydrochlorothiazide' s tmax.