大黄酸的HPLC-荧光检测及其在人体药代动力学中的应用  

Determination of rhein in plasma,urine and feces by HPLC-fluorescence detection and its pharmacokinetics in healthy volunteers

作　　者：万萍[1] 孙建国[1] 郝刚[1] 张筱璇[1] 肖大伟[2] 刘志红[3] 王广基[1] 

机构地区：[1]中国药科大学江苏省药物代谢动力学重点实验室,南京210009 [2]南京大学医学院附属医院鼓楼医院Ⅰ期临床研究室,南京210008 [3]南京军区南京总医院全军肾脏病研究所,南京210002

出　　处：《中国药科大学学报》2013年第1期73-76,共4页Journal of China Pharmaceutical University

基　　金：国家"重大新药创制"科技重大专项资助项目(No.2008ZX09101-050);江苏省科技基础设施建设计划资助项目(No.BM2012012)~~

摘　　要：建立大黄酸在健康志愿者血浆及尿粪中的HPLC-荧光检测方法(HPLC-FLD),色谱柱为Hypersil C18(25 cm×4.6 mm,2.5μm),流动相为甲醇-乙腈-1%冰醋酸(61∶15∶24),柱温为40℃,内标为1,8-二羟基蒽醌,检测激发波长为440 nm,发射波长为520 nm。在所建立的色谱条件下,大黄酸与各杂质分离良好,在血浆、尿、粪中线性范围分别为0.05～10.00μg/mL,0.10～25.00μg/mL,0.20～100.00μg/mL,最低定量限分别为0.05,0.10和0.20μg/mL。健康受试者单次口服200 mg大黄酸后,血药浓度-时间曲线呈二房室模型。主要药代动力学参数cmax,tmax,AUC0-∞,t1/2以及MRT分别为(16.0±3.4)μg/mL,(4.0±0.6)h,(152.7±45.7)μg.h/mL,(5.5±1.1)h以及(8.9±2.2)h;原药大黄酸在尿、粪中累积排泄分数分别为(8.19±1.84)%和11.00%。该法操作简便、灵敏,适用于对微量生物样品进行大批量测定。This study established a HPLC-fluorescence detection（HPLC-FLD） assay for determining of rhein in human plasma, urine and feces on a reversed-phase C18 column with a mobile phase of methanol-aeetonitrile-1% acetic acid （61 ： 15 ： 24）. HPLC-FLD was performed at excitation wavelength 440 nm and emission wavelength 520 nm for rhein and the internal standard. Calibration curves were linear over the ranges of 0. 05-10. 00μg/mL in plasma, 0. 10-25.00 μg/mL in urine and 0. 20-100. 00μg/mL in feces. The lowest limit of quantification for rhein was 0. 05 μg/mL in plasma, 0. 10 μg/mL in urine and 0. 20 μg/mL in feces. The recovery of this method was greater than 80%. The main pharmacokinetic parameters c t AUC0-∞, tl/2 and MRT were （ 16. 0 ± 3.4）μg/mL, （4. 0 ±0. 6） h, （ 152.7 ±45.7） μg·h/mL, （5.5 ± 1.1） h and （8.9 ±2. 2） h, respectively. The accumu- lative excretion rate of rhein in urine and feces were （8.19 ± 1.84） % and 11.00%, separately. This assay was proved to be convenient, accurate, sensitive and suitable for mass determination of biological samples.

关 键 词：大黄酸 HPLC-荧光检测法 药代动力学 累积排泄分数 

分 类 号：R969.1[医药卫生—药理学]