Development of high-performance liquid chromatography assay for pharmacokinetic analysis of KCNQ/M-channel opener QO58-lysin in rat plasma  

高效液相色谱法测定大鼠血浆中新型KCNQ/M通道开放剂QO58-lysin浓度的方法学建立与优化及其药代动力学研究（英文）

作　　者：马天阳[1,2] 滕博川 祁金龙[3] 张海林[3] 王克威[1,2,4] 

机构地区：[1]北京大学医学部药学院天然药物及仿生药物国家重点实验室 [2]分子与细胞药理学系,北京100191 [3]河北医科大学药理学系,石家庄050017 [4]北京大学麦戈文脑科学研究所,北京100871

出　　处：《Journal of Chinese Pharmaceutical Sciences》2014年第3期153-158,共6页中国药学（英文版）

基　　金：Ministry of Science and Technology of China(Grant No.2013ZX09103001-015 and 2013CB531300);the National Science Foundation of China(Grant No.81221002)

摘　　要：A simple, reliable and efficient assay for quantitative analysis of a novel Kv7/KCNQ/M-channel opener QO58-lysin in rat plasma was developed using high-performance liquid chromatography（HPLC） with UV detection. Separation of compound QO58-lysin from plasma was achieved using a reverse-phase C18 column with a mobile phase of 0.2 M ammonium acetate in H2O–acetonitrile（40：60, v/v） with nitrendipine used as an internal standard（IS）. The retention times of QO58-lysin and the IS in rat plasma were 3.8 and 5.4 min, respectively. Calibration curve was linear ranging from 0.1 to 120 μg/mL with correlation coefficient（r2） of 0.9996. The lower limit of quantification was 0.1 μg/mL. Accuracy, precision, recovery as well as stability were all within acceptable criteria according to Food and Drug Administration（FDA） guidelines. This validated assay was successfully applied to determine the pharmacokinetics of QO58-lysin administered intravenously（10 mg/kg） in SD rats. The distribution and elimination half-life of QO58-lysin in plasma was（0.25±0.16） h and（2.15±0.12） h, respectively.本研究建立了一种简单、可靠、高效的定量检测电压门控KCNQ/M钾通道开放剂QO58-lysin在大鼠血浆中浓度的方法。采用高效液相色谱与紫外检测器,使用反相C18色谱柱,以0.2 M的乙酸铵–乙腈(40:60,v/v)为流动相,尼群地平(nitrendipine)为内标物。QO58-lysin与尼群地平的色谱峰保留时间分别为3.8 min与5.4 min。QO58-lysin在0.1–120μg/mL浓度范围内具有良好线性(r2=0.9996),最低检测浓度为0.1μg/mL。根据FDA指南,检测方法的准确度、精密度、回收率与稳定性皆符合要求。该方法成功应用于测定SD大鼠单剂量尾静脉注射QO58-lysin(10 mg/kg)的药代动力学研究。化合物QO58-lysin在大鼠血浆的半衰期和消除半衰期分别为(0.25±0.16)h和(2.15±0.12)h。

关 键 词：KCNQ opener QO58-lysin HPLC PHARMACOKINETICS 

分 类 号：R969.1[医药卫生—药理学]