HPLC分析大鼠血浆中β-蜕皮甾酮浓度及其初步药代动力学研究  

Plasma concentration of β-ecdysterone determined by HPLC and its preliminary pharmacokinetics in rats

作　　者：朱裕林[1] 戴浩志 桑冉[1] 孔令提[1] 许健[1] 张盛[2] 陈卫东[2] ZHU Yulin;DAI Haozhi;SANG Ran;KONG Lingti;XU Jian;ZHANG Sheng;CHEN Weidong(Department of Pharmacy,First Affiliated Hospital of Bengbu Medical College,Bengbu 233004,China;Anhui University of Chinese Medicine)

机构地区：[1]蚌埠医学院第一附属医院药剂科,蚌埠233004 [2]安徽中医药大学

出　　处：《山西医科大学学报》2019年第11期1598-1602,共5页Journal of Shanxi Medical University

基　　金：安徽省自然科学基金青年基金资助项目(1608085QH213)

摘　　要：目的采用HPLC建立大鼠血浆中β-蜕皮甾酮浓度的测定方法,并探究β-蜕皮甾酮在大鼠体内的初步药代动力学情况。方法以安替比林为内标,色谱柱Unitary C18(4. 6 mm×150 mm,5μm),流动相为乙腈-0. 1%甲酸(16∶84),流速1. 0 ml/min,柱温30℃,进样量20μl,紫外检测波长为263 nm,建立大鼠血浆中β-蜕皮甾酮的分析方法。大鼠灌胃β-蜕皮甾酮10 mg/kg,测定不同时间点β-蜕皮甾酮血药浓度。运用DAS 2. 1软件进行数据分析,得出其主要药动学参数。结果大鼠血浆中β-蜕皮甾酮在0. 25-100. 00μg/ml浓度范围内线性关系良好(Y=0. 841X-0. 011 4,R2=0. 999 0),定量下限0. 25μg/ml,日内和日间精密度、稳定性RSD均小于10%,低、中、高浓度(0. 50,20. 00,75. 00μg/ml)血浆样品回收率分别为(89. 72±5. 71)%,(90. 60±5. 01)%,(97. 69±1. 44)%,符合生物样品分析要求。主要药动学参数峰浓度Cmax为(66. 41±4. 65)μg/ml,消除半衰期t1/2(β)为(1. 79±0. 11) h,总清除率CL为(0. 40±0. 02) L/(h·kg),0-24 h药时曲线下面积AUC0-24为(252. 30±11. 84)μg/(ml·h)。结论本研究建立的体内β-蜕皮甾酮HPLC检测方法操作快速、线性良好、准确度高,可应用于β-蜕皮甾酮在大鼠体内的药代动力学研究。Objective To develop a HPLC method in the determination of β-ecdysterone in rat plasma and investigate the initial pharmacokinetics of β-ecdysterone in rats. Methods Antipyrine was used as the internal standard on a Unitary C18( 4. 6 mm × 150 mm,5 μm),acetonitrile-0. 1% formic acid( volume ratio 16 ∶ 84) was used as the mobile phase,the flow rate was 1. 0 ml/min,the column temperature was 30 ℃,the injection volume was 20 μl,and the detection wavelength was 263 nm. According to the conditions,a method was established to analyze β-ecdysterone in plasma. Rats were intragastrically administered with 10 mg/kg β-ecdysterone to determine plasma concentrations at different time points. The data obtained were analyzed with DAS 2. 1 software,and the main pharmacokinetic parameters were obtained. Results The linear relationship of β-ecdysterone in plasma was well within the range of 0. 25-100. 00 μg/ml( Y = 0. 841 X-0. 011 4,R2= 0. 999 0). The lower limit of quantification was 0. 25 μg/ml,and the intra-day and interday precision,and stability RSD were all less than 10%. The recoveries of low,medium,and high concentration plasma samples( 0. 50,20. 00,75. 00 μg/ml) were 89. 72%±5. 71%,90. 60%±5. 01%,97. 69%±1. 44%,respectively,which met the requirements for biological sample analysis. The main pharmacokinetic parameter Cmaxwas( 66. 41 ±4. 65) μg/ml,t1/2( β)was( 1. 79 ±0. 11) h,CL was( 0. 40 ±0. 02) L/( h·kg),and AUC0-24 was( 252. 30 ±11. 84) μg/( ml·h). Conclusion The HPLC method established in this experiment is quick,linear and accurate,and can be used for the analysis of plasma β-ecdysterone concentration and its pharmacokinetics in rats.

关 键 词：β-蜕皮甾酮 HPLC 血药浓度 药代动力学 

分 类 号：R969[医药卫生—药理学]