LC-MS/MS法测定犬体内托拉塞米浓度及相对生物利用度研究

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (2): 199-205.

LC-MS/MS法测定犬体内托拉塞米浓度及相对生物利用度研究

李瑞兴^1,2, 樊慧蓉², 魏广力², 任晓文², 司端运², 刘昌孝²

¹天津中医药大学,天津 300193;
²天津药物研究院,释药技术与药代动力学国家重点实验室, 天津 300193

收稿日期:2011-08-19 修回日期:2011-10-31 出版日期:2012-02-26 发布日期:2012-03-12
通讯作者: 司端运,男,研究员,研究方向:药代动力学。Tel: 022-84845261 E-mail: ddysi@sohu.com
作者简介:李瑞兴,男,硕士研究生,研究方向:药代动力学。Tel: 15222899139 E-mail: hawk_pha@163.com
基金资助:
国家973项目(2010CB735602)

LC-MS/MS determination of torasemide in Beagle dog plasma and bioavailability evaluation

LI Rui-xing^1,2, FAN Hui-rong², WEI Guang-li², REN Xiao-wen², SI Duan-yun², LIU Chang-xiao²

¹Tianjin University of Traditional Chinese Medicine, Tianjin 300193, Tianjin,China;
²State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, Tianjin,China

Received:2011-08-19 Revised:2011-10-31 Online:2012-02-26 Published:2012-03-12

摘要/Abstract

摘要： 目的: 建立LC-MS/MS法测定Beagle犬体内托拉塞米的浓度,并研究托拉塞米缓释片的相对生物利用度。方法: 色谱柱为Waters Symmetry-C₁₈(100 mm×4.6 mm, 5 μm);流动相为甲醇∶20 mmol/L 甲酸铵(65∶35,V∶V);流速 0.4 mL/min;柱温 30 ℃。采用两制剂双周期随机交叉试验设计,分别给予6只Beagle犬受试制剂或参比制剂 5 mg,采用LC-MS/MS法测定给药后不同时间的血药浓度。结果: 托拉塞米线性范围为 0.02~5 μg/mL,最低定量限为 0.02 μg/mL,分析方法灵敏、稳定、特异性高。受试制剂和参比制剂的主要药动学参数:峰浓度(C_max)、达峰时间(t_max)和药-时曲线下面积(AUC_{0-48 h})分别为(2.6±0.5) g/mL 和 (3.0±0.6) g/mL、(3.3±1.4) h 和(1.2±0.8) h、(36.1±11.0) g·h·mL^-1和(32.1±13.1) g·h·mL^-1。以AUC_{0-48 h}计算,受试制剂的相对生物利用度F为(118.0±28.3)%。结论: 该方法操作简单、准确、重复性好,并成功地运用于犬体内托拉塞米相对生物利用度的研究。

关键词: 托拉塞米, LC-MS/MS, 相对生物利用度

Abstract: AIM: To establish an LC-MS/MS method for the determination of torasemide in Beagle dog plasma,and study the relative bioavailability of the torasemide sustained release tablets.METHODS: A reversed phase HPLC column of Waters Symmetry-C₁₈ (100 mm×4.6 mm, 5 μm) was used in the experiment.Acetonitrile-20 mmol/L ammonium formate (65∶35,V/V) was used as mobile phase at the flow rate of 0.4 mL/min, the column temperature was set at 30 ℃. A single oral dose of 5 mg torasemide release tablets or reference tablets were given to 6 Beagle dogs in an open randomized two way crossover design.The concentrations of plasma samples collected at the different time were determined by LC-MS/MS method.RESULTS: With the linear range of 0.02-5 μg/mL and the lower limit quantification of 0.02 μg/mL, the LC-MS/MS method had high sensitivity, stability and specificity. The main pharmacokinetic parameters of test sustained release tablets and reference tablets were as follows:the C_max were (2.6±0.5) μg/mL and (3.0±0.6) g/mL,the t_max were (3.3±1.4) h and (1.2±0.8) h,the AUC_{0-48 h} were (36.1±11.0) μg·h·mL^-1 and (32.1±13.1) μg·h·mL^-1. Compared to regular tablets,the bioavailability of sustained release tablets was (118.0±28.3)%.CONCLUSION: The method is simple, accurate and robust for the determination of torasemide in Beagle dog plasma, and successfully applied it to the bioavailability evaluation of torasemide sustained release tablets given to Beagle dogs.

Key words: Torasemide, LC-MS/ MS, Relative bioavailability

中图分类号:

R969.1

李瑞兴, 樊慧蓉, 魏广力, 任晓文, 司端运, 刘昌孝. LC-MS/MS法测定犬体内托拉塞米浓度及相对生物利用度研究[J]. 中国临床药理学与治疗学, 2012, 17(2): 199-205.

LI Rui-xing, FAN Hui-rong, WEI Guang-li, REN Xiao-wen, SI Duan-yun, LIU Chang-xiao. LC-MS/MS determination of torasemide in Beagle dog plasma and bioavailability evaluation[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(2): 199-205.

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