代谢分析

大鼠血浆中大麻二酚超高效液相色谱-三重四极杆质谱法检测及代谢动力学研究

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  • 滨州医学院药学院,烟台 264003
第一作者 Tel:17865582693;E-mail:xinzhenfu3@163.com
*张淑敏 Tel:(0535)3800001;E-mail:klj1182@163.com;shumin_zhang@outlook.com
寇立娟 Tel:150198689241;E-mail:xinzhenfu3@163.com

收稿日期: 2020-12-11

  网络出版日期: 2024-07-15

Determination of cannabidiol and its pharmacokinetics in rat plasma by ultra performance liquid chromatography-triple quadrupole mass spectrometry

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  • School of Pharmacy,Binzhou Medical University,Yantai 264003,China

Received date: 2020-12-11

  Online published: 2024-07-15

摘要

目的:建立了沉淀蛋白法结合超高效液相色谱-三重四极杆质谱法灵敏检测大鼠血浆中大麻二酚的分析方法,并将此方法成功应用于大麻二酚在大鼠血浆中的代谢动力学研究。方法:室温状态下乙腈为蛋白沉淀剂,血浆-乙腈(1∶3)作为最佳提取条件;采用Waters ACQUITY HSS T3(10 mm×2.1 mm,1.7 μm) 色谱柱进行分离,以乙腈-5 mmol·L-1 乙酸铵为流动相进行等度洗脱,在电喷雾负离子模式下,采用多反应监测模式进行定性定量分析。结果:大麻二酚质量浓度在2.5~1 500 ng·mL-1 范围内呈现良好线性(r2≥ 0.998),定量下限为2.5 ng·mL-1;方法批内精密度与批间精密度均小于15%,准确度RE 在±12% 以内; 方法提取回收率在96.1%~100.1%;血浆样品短期稳定性、长期反复冻融稳定性良好;大鼠单次灌胃大麻二酚芝麻油样品后,血浆中达峰浓度为70.4 ng·mL-1,口服绝对生物利用度为22.6%。结论:建立的方法准确度高、灵敏度高、样品前处理方法简单、快速,该方法为大麻二酚的新剂型与新给药系统开发提供 参考。

本文引用格式

付信珍, 谢则平, 李志, 郭琳, 刘明, 张淑敏, 寇立娟 . 大鼠血浆中大麻二酚超高效液相色谱-三重四极杆质谱法检测及代谢动力学研究[J]. 药物分析杂志, 2021 , 41(9) : 1513 -1518 . DOI: 10.16155/j.0254-1793.2021.09.04

Abstract

Objective: To establish a method for determination of cannabidiol in pharmacokinetics study of rat plasma based on protein precipitation coupled with ultra performance liquid chromatography-triple quadrupole mass spectrometry. Methods: Cannabidiol was effectively extracted by acetonitrile with a ratio of plasma-acetonitrile (1∶3),and was separated with a Waters ACQUITY HSS T3 column (100 mm×2.1 mm,1.7 μm) using acetonitrile-5 mmol·L-1 ammonium acetate (80∶20) as the mobile phase. Under the electrospray negative ion mode,the multi-reaction monitoring mode was used for qualitative and quantitative analysis of cannabidiol. Results: The results indicated that cannabidiol in plasma had a good linear relationship in a range of 2.5-1 500 ng·mL-1(r2≥ 0.998). The lower detection limit was 2.5 ng·mL-1. The intra-and inter-batch precision were less than 15%,the accuracy RE was within ±12% and the average recoveries was 96.1%-100.1% for spiked plasma. The matrix effect and plasma stability could meet methodological requirements for biological sample analysis. The established method was successfully used in pharmacokinetics of cannabidiol in rat plasma. The results showed Cmax in plasma was 70.4 ng·mL-1 and oral relative bioavailability was 22.6%. Conclusion: This method is accurate,sensitive,simple and fast. It can help the development of new drug delivery systems for cannabidiol.

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