Concentration Determination of Nateglinide in Rats'Plasma by UPLC and Study on Its Pharmacokinetics / 中国药房

ABSTRACT

OBJECTIVE:To establish a method for the concentration determination of nateglinide in rats'plasma and study its pharmacokinetic characteristics in rats in vivo. METHODS:UPLC was performed on the column of Acquity UPLC? BEH C18 with mobile phase of acetonitrile-10 mmol/L potassium dihydrogen phosphate buffer(4159,V/V)at flow rate of 0.38 mL/min,with col-umn temperature of 35 ℃,detection wavelength of 210 nm and volume of 2 μL. 18 Wister rats were intragastrically administrated nateglinide 16 mg/kg. Blood sample 0.4 mL was taken from medial canthus before administration and after 10,20,30,45,60, 90,120,180,240,360,480 min of administration. The concentration of nateglinide in rats'plasma was determined;then DAS 2.1.1 software was used to calculate its pharmacokinetic parameters. RESULTS:Nateglinide showed good linear relationship in 0.05-6.4μg/mL(r=0.9993),lower limit of quantification was 0.05μg/mL;RSDs of inter-day(n=5),intra-day(n=3)and sta-bility (n=3) tests were lower than 10%;extraction recovery rate and method recovery rate were 78.71%-80.56%,91.78%-100.42%(RSD<10%,n=5),respectively. After rats were intragastrically administrated nateglinide,AUC0-8 h was (5.87 ± 2.32)μg·h/mL,AUC0-∞was(6.11±2.48)μg·h/mL,t1/2 was(1.72±0.55)h,tmax was(0.67±0.29)h and cmax was(3.34±1.23)μg/mL. CONCLUSIONS:The method is accurate,rapid with strong specificity,and can be used for the concentration determination of nat-eglinide in rats in vivo;nateglinide is absorbed and metabolized quickly in rats in vivo.