利巴韦林的含量测定以及人体药代动力学分析

doi:10.5246/jcps.2013.04.052

利巴韦林的含量测定以及人体药代动力学分析

张华, 王桂玲, 李可欣, 张烜^*, 张强

1. 北京大学医学部药学院药剂学系, 北京 100191
2. 卫生部北京医院药剂科, 北京 100730

收稿日期:2012-10-09 修回日期:2012-11-19 出版日期:2013-07-10 发布日期:2013-07-10
通讯作者: 张烜*

A high performance liquid chromatography method for the quantitative
determination of ribavirin in human plasma and its application in a pharmacokinetics study

Hua Zhang, Guiling Wang, Kexin Li, Xuan Zhang^*, Qiang Zhang

1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Department of Pharmacy, Beijing Hospital, Ministry of Health, Beijing 100730, China

Received:2012-10-09 Revised:2012-11-19 Online:2013-07-10 Published:2013-07-10
Contact: Xuan Zhang*

摘要/Abstract

摘要：

本文建立了简单、快速的HPLC方法测定利巴韦林在人血浆中的含量, 并研究了健康受试者体内利巴韦林片剂的药代动力学。HPLC方法选择C18色谱柱(250 mm×4.6 mm, 5 μm), 超纯水为流动相, 柱温为25 °C, 检测波长为207 nm。在50.4-2016.0 ng/mL范围内线性关系良好(r = 0.9998), 最低检测浓度为15 ng/mL。低、中、高三个浓度的相对回收率大于90%, 日内精密度小于10%, 日间精密度小于15%。用药代动力学软件WinNonlin进行房室模型分析的结果显示: 二室模型能更好地模拟利巴韦林在体内的过程。计算得到的AUC0-t 、CL/F和Cmax分别是10807.8 h∙ng/mL、 64879.5 mL和 525.1 ng/mL。这些结果为药剂工作者开发利用利巴韦林剂型提供了参考。

关键词: 利巴韦林, 高效液相色谱法, 药代动力学, 房室模型

Abstract:

The clinical pharmacokinetics of ribavirin after a single oral dose of 600 mg ribavirin tablets in healthy Chinese volunteers was studied. A rapid and simple high performance liquid chromatography (HPLC) method was developed to determine the ribavirin concentration in human plasma. C18 column was used for separation with a column temperature of 25 °C, the mobile phase was ultrapure water adjusted to pH 3 with acetic acid at the flow rate of 1 mL/min, and the detection wavelength was set at 207 nm. The linear range of the standard curves was 50.4-2016.0 ng/mL and the lower limit of quantification (LLOQ) was 50.4 ng/mL. The relative recoveries of ribavirin were more than 90% in plasma. The RSD of the intra-day precision was less than 10% and that of inter-day was less than 15%. The pharmacokinetic parameters of ribavirin were calculated by WinNonlin. Results indicated that the two-compartment model was a better model for describing the pharmacokinetics profile of ribavirin than one-compartment model. The AUC0-t was 10807.8 h∙ng/mL, the CL/F was 64879.5 mL, and the Cmax was 525.1 ng/mL. These results provided the experimental data for the development of ribavirin dosage form.

Key words: Ribavirin, HPLC, Pharmacokinetics, Compartmental model

中图分类号:

R917.1

Supporting: ^*Corresponding author. Tel.: 86-10-82802683

张华, 王桂玲, 李可欣, 张烜^*, 张强. 利巴韦林的含量测定以及人体药代动力学分析[J]. , DOI: 10.5246/jcps.2013.04.052.

Hua Zhang, Guiling Wang, Kexin Li, Xuan Zhang^*, Qiang Zhang. A high performance liquid chromatography method for the quantitative
determination of ribavirin in human plasma and its application in a pharmacokinetics study[J]. , DOI: 10.5246/jcps.2013.04.052.

[1]	杨杰, 景彩芳, 李少创, 刘思彤, 李董明, 李钦青, 贺文彬. 复方党参颗粒制备工艺优化及4种成分的同时测定[J]. 中国药学(英文版), 2023, 32(8): 665-676.
[2]	杨雁芳, 韦玮, 张雷, 徐嵬, 杨秀伟. UPLC-MS/MS法测定都梁丸中37个成分在大鼠体内的药代动力学[J]. 中国药学(英文版), 2023, 32(7): 560-573.
[3]	李莹, 文周, 刘永玲, 赵治兵, 王磊, 程泽能. 高效液相色谱法测定大鼠血浆中阿昔洛韦浓度及其与吉非替尼药物相互作用的研究[J]. 中国药学(英文版), 2021, 30(6): 495-504.
[4]	李晓娇, 栾树鑫, 张洪, 万洪泉, 陈红, 刘成娇, 刘畅, 丁艳华. 单剂量长效利培酮注射液在中国精神分裂症患者体内的药代动力学、药效学和安全性研究[J]. 中国药学(英文版), 2021, 30(3): 206-217.
[5]	周艳, 宋恒文, 邵志超, 尹博民, 付西美, 谢典佑, 韦利军. 一种新的细胞周期蛋白依赖性激酶(CDK)9抑制剂QHRD107对急性髓系白血病的临床前疗效[J]. 中国药学(英文版), 2021, 30(2): 146-156.
[6]	杨秀伟, 张友波, 徐嵬. 静脉和灌胃给予大鼠茴香酸对羟基苯乙酯的RP-HPLC法测定和药代动力学研究[J]. 中国药学(英文版), 2020, 29(11): 804-812.
[7]	杨辉, 胡小鹏, 杨晓勇, 刘航, 任亮, 王玮, 刘丽宏, 张小东. 肾移植术后糖皮质激素和他克莫司的药代动力学相互作用[J]. 中国药学(英文版), 2019, 28(4): 257-263.
[8]	刘鑫, 张波, 梅丹, 黄凯. HPLC-MS/MS法测定大鼠血浆中异绿原酸B浓度及其在药代动力学研究中的应用[J]. 中国药学(英文版), 2019, 28(3): 167-173.
[9]	张玲玲, 张慧文, 武世奎, 刘宏, 李静媛, 董馨, 夏慧敏, 王焕芸. UPLC-Q-Exactive-MS 同时测定三臣丸中六种活性成分的药代动力学研究[J]. 中国药学(英文版), 2019, 28(11): 812-824.
[10]	欧阳文鹃, 张亚兰, 徐平声, 戴智勇, 马虹英, 秦群. 国产注射用甲磺酸帕珠沙星在健康人体的药代动力学研究[J]. 中国药学(英文版), 2019, 28(1): 40-48.
[11]	常馨予, 郭桂明, 范峥, 王宏蕾, 刘洋, 韩丽娟. UPLC-MS/MS法测定黄芪桂枝五物汤在大鼠血浆中两种活性成分及药代动力学研究[J]. 中国药学(英文版), 2018, 27(4): 263-272.
[12]	姜华, 杨景明, 曹玲, 贾桂枝, 戴红良, 孟祥才. 高温胁迫对防风药材药代动力学和药效的影响[J]. 中国药学(英文版), 2018, 27(2): 109-115.
[13]	王环鑫, 孙亚欣, 徐善森, 路童, 陈亚南, 肇丽梅. 高效液相色谱法测定人血浆中游离拉莫三嗪的血药浓度[J]. 中国药学(英文版), 2018, 27(12): 832-839.
[14]	代华灵, 高伟祺, 张国顺, 王锐利, 张淑秋. 青蒿素脂质纳米粒的制备及药动学评价[J]. 中国药学(英文版), 2017, 26(3): 180-186.
[15]	费文波, 梁晓霞, 何敏. 不同藏医炮制方法对诃子中诃子酸含量的影响[J]. 中国药学(英文版), 2017, 26(3): 230-234.