UPLC法测定大鼠血浆中那格列奈的浓度及药动学研究
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篇名: UPLC法测定大鼠血浆中那格列奈的浓度及药动学研究
TITLE:
摘要: 目的:建立测定大鼠血浆中那格列奈浓度的方法,并研究其在大鼠体内的药动学特征。方法:采用超高效液相色谱法(UPLC)。色谱柱为Acquity UPLC® BEH C18,流动相为乙腈-10 mmol/L磷酸二氢钾缓冲盐溶液(41 ∶ 59,V/V),流速为0.38 mL/min,柱温为35 ℃,检测波长为210 nm,进样量为2 μL。18只Wistar大鼠分别ig那格列奈16 mg/kg,分别于给药前及给药后10、20、30、45、60、90、120、180、240、360、480 min于眼内眦取血0.4 mL,测定血浆中那格列奈的浓度;并采用DAS 2.1.1软件计算那格列奈药动学参数。结果:那格列奈质量浓度在0.05~6.4 μg/mL范围内线性关系良好(r=0.999 3),定量下限为0.05 μg/mL;日内(n=5)、日间(n=3)精密度和稳定性(n=3)试验的RSD均小于10%;提取回收率和方法回收率分别为78.71%~80.56%、91.78%~100.42%(RSD<10%,n=5)。大鼠ig那格列奈后,AUC0-8 h为(5.87±2.32) μg·h/mL,AUC0-∞为 (6.11±2.48) μg·h/mL,t1/2为(1.72±0.55) h,tmax为(0.67±0.29) h,cmax为(3.34±1.23) μg/mL。 结论:该方法准确快速、专属性强,可用于大鼠体内那格列奈浓度的测定;那格列奈在大鼠体内吸收迅速、代谢较快。
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 (41 ∶ 59, V/V) at flow rate of 0.38 mL/min, with column 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 0.05-6.4 μg/mL (r=0.999 3), lower limit of quantification was 0.05 μg/mL; RSDs of inter-day (n=5) , intra-day (n=3) and stability (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 nateglinide in rats in vivo; nateglinide is absorbed and metabolized quickly in rats in vivo.
期刊: 2017年第28卷第31期
作者: 王凯,蒋大鹏,张伟,王淑梅
AUTHORS: WANG Kai,JIANG Dapeng,ZHANG Wei,WANG Shumei
关键字: 那格列奈;超高效液相色谱法;药动学;大鼠
KEYWORDS: Nateglinide; UPLC; Pharmacokinetics; Rats
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