固相萃取结合柱前衍生化RP-HPLC法测定人血浆中的卡托普利的浓度及其药动学与相对生物利用度研究

固相萃取结合柱前衍生化RP-HPLC法测定人血浆中的卡托普利的浓度及其药动学与相对生物利用度研究

丁劲松, 张毕奎, 李焕德, 刘义钊, 邓航

1.中南大学湘雅二医院, 长沙 410011;
2.湖南常德第一人民医院, 常德 415700;
3.桂林医学院附属医院, 桂林 510012

收稿日期:2001-02-19 修回日期:2001-06-06 出版日期:2001-09-15 发布日期:2001-09-15

HPLC Determination of Captopril in Human Plasma with Pre-column Derivation and Solid-phase Extraction and Studies on Its Pharmacokinetic and Relative Bioavailability

Ding Jinsong, Zhang Bikui, Li Huande, Liu Yizhao, Deng Hang

1. The Second Affiliated Hospital of Xiangya Medical College, Central South University, Changsha 410011;
2. The First people Hospital of Hu'nan Changde, Changde 415700;
3. The Affiliated Hospital of Guilin Medical College, Guilin 510012

Received:2001-02-19 Revised:2001-06-06 Online:2001-09-15 Published:2001-09-15

摘要/Abstract

摘要： 本文建立固相萃取结合柱前衍生化测定人血浆中的卡托普利浓度的RP-HPLC法, 并利用该方法研究两种国产卡托普利片在健康受试者中的药物动力学与相对生物利用度。以对溴苯乙酰基溴(p-BPB) 为衍生化试剂, 衍生化产物经固相萃取后由VP-ODS 柱分离测定, 流动相为乙腈-水-冰醋酸(100:150:1.25) (v/v), 紫外检测波长为257 nm, 线性范围为5~1000 ng·mL^-1, (r = 0.9987), 平均回收率为98.65±2.04%, 日内和日间RSD 分别小于3.4% 和8.4%。以自身对照随机交叉方式, 单计量分别给予18名健康男性志愿者两种国产卡托普利片50 mg, 卡托普利在人体内符合一室开放模型。两种卡托普利片的AUC0-T, Cmax和Tmax分别为424.5±125.7 μg·h·L^-1和439.4±113.3 μg·h·L^-1, 505.9±244.6 μg·L^-1和504.8±172.2 μg·L^-1, 0.662±0.181 h和0.528±0.176 h。两种制剂间的各参数无明显差异, 双单侧t检验结果表明二者为生物等效制剂, 其相对生物利用度为96.1±14.6%。

关键词: 卡托普利, 固相萃取, HPLC, 药动学, 生物利用度

Abstract: A new pre-column derivation HPLC method with solid-phase extraction to determine captopril in human plasma was established. Derivation products were extracted by a solid-phase extraction method after the reagent, p-α-dibromoacetophenone (p-BPB), was added in the plasma samples. The samples were analyzed in a VP-ODS column with UV-detector. The calibration curve of captopril was linear within the range of 5~1000 g·mL^-1 with r = 0.9987, the recovery of this method was 98.65±2.04%, within day and between day RSD were no more than 3.4% and 8.4% respectively. To study the pharmacokinetics and the relative bioavailability of captopril tablets, two formulations of captopril tablets were given to 18 healthy male volunteers according to a randomized 2-way cross-over design with a 1-week washout period. The respective AUC0~6, Cmax and Tmax values of the two formulations were 424.5±125.7 and 439.4±113.3 μg·h·L^-1; 505.9±244.6 and 504.8±172.2 μg·L^-1; 0.662±0.181 and 0.528±0.176 h. Results from statistics analysis showed that there were no significant difference between the AUC0~6, Cmax and Tmax values of the two formulations, The relative bioavailability of tablets I with respect to II was 96.1±14.6% from AUC0~6 measurement. Bioequivalance was observed between the two tablets.

Key words: Captopril, Solid-Phase Extraction, HPLC, Pharmacokinetics, Bioavailability

Supporting:

丁劲松, 张毕奎, 李焕德, 刘义钊, 邓航. 固相萃取结合柱前衍生化RP-HPLC法测定人血浆中的卡托普利的浓度及其药动学与相对生物利用度研究[J]. .

Ding Jinsong, Zhang Bikui, Li Huande, Liu Yizhao, Deng Hang . HPLC Determination of Captopril in Human Plasma with Pre-column Derivation and Solid-phase Extraction and Studies on Its Pharmacokinetic and Relative Bioavailability[J]. .

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