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毕业论文网 > 毕业论文 > 化学化工与生命科学类 > 药学 > 正文

HPLC-MSMS法检测大鼠血浆中汉防己甲素的药物浓度及其药代动力学研究毕业论文

 2022-06-12 20:38:12  

论文总字数:17012字

摘 要

建立了一种快速、灵敏的液相色谱-质谱串联(LC/MS/MS)方法测定大鼠血浆中汉防己甲素的含量, 方法已充分验证,并被成功地应用于SD大鼠单次给药后体内药代动力学研究。通过乙酸乙酯液液萃取处理样品。汉防己甲素和阿霉素(内标)通过BDS HYPERSIL-C8 柱分离,流动相为5 mmoL·L-1 乙酸铵-乙腈(54:46,V/V),含0.3%甲酸。浓度测定是在三重四极质谱的多反应监测模式下进行。离子优化利用ESI离子源( )和选择性使用MS / MS分析实现,汉防己甲素和内标的离子对分别是m/z 623.1→381.8和m/z 544.4→397.6。这种定量分析大鼠血浆中汉防己甲素的方法在浓度范围是0.5~400 ng·mL-1,,具有良好的线性,定量下限为0.5 ng·mL-1。准确度(RE)是在-0.4%~2.6%之间,日内和日间精密度(RSD)分别在4.6%~7.3%和3.9%~4.9%。分析无内源性化合物的干扰,并且汉防己甲素在整个试验期间是稳定的。该方法已成功应用于汉防己甲素以2.5mg·kg-1 剂量对大鼠单次尾静脉注射给药的药代动力学研究,结果证实这种方法满足汉防己甲素的药代动力学研究的要求。

关键词:LC/MS/MS 汉防己甲素 药代动力学

Establishment of a liquid chromatographic/mass spectrometry method for quantification of tetrandrine in rat plasma and its application to pharmacokinetic study

Abstract

A rapid and sensitive liquid chromatography-tandem mass spectrometric method (LC/MS/MS) for the determination of tetrandrine in rat plasma has been developed, fully validated and successfully applied to pharmacokinetic study in Sprague–Dawley (SD) rats after a single oral administration.Sample preparation involves a liquid–liquid extraction with ethyl acetate. Tetrandrine and Doxorubicin (internal standard) were well separated by LC with a BDS HYPERSIL-C8 column using 5 mmoL·L-1 ammonium acetate-acetonitrile solution (54:46,V/V) containing 0.4% formic acid as mobile phase. Detection was performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. The ionization was optimized using ESI( ) and selectivity was achieved using MS/MS analysis, m/z 623.1→381.8 and m/z 544.4→397.6 for tetrandrine and I.S., respectively. The present method exhibited good linearity over the concentration range of 0.5~400 ng·ml-1 for tetrandrine in rat plasma with a lower limit of quantification of 0.55 ng·ml-1. The accuracy ranged from -0.4% to 2.6%,the intra- and inter-day precision were from 4.6% to 7.3% and from 3.9% to 4.9%, respectively.No endogenous compounds were found to interfere with the analysis,and tetrandrine was stable during the whole assay period. The method was successfully applied to a pharmacokinetic study after a tail intravenous injection administration of tetrandrine to SD rats with a single dose of 2.5mg·kg-1. The results confirm that the assay is suitable for the pharmacokinetic study of tetrandrine.

Keywords:LC/MS/MS;tetrandrine;Pharmacokinetics

目 录

摘 要 Ⅰ

Abstract Ⅱ

第一章 文献综述 1

1.1 汉防己甲素的药理及药效作用 2

1.2汉防己甲素药代动力学研究概况 3

1.3汉防己甲素分析方法研究进展 4

1.4总结 4

第二章 实验 5

2.1 化学药品和试剂 5

2.2 实验动物 5

2.3 LC / MS / MS条件与评价 6

2.4 溶液配制 6

2.5 血浆样品的处理 6

2.6 药代动力学研究 7

2.7 方法验证 7

第三章 结果与讨论 9

3.1 LC / MS / MS方法 9

3.2 验证方法 9

3.2.1 标准曲线和最低定量限 9

3.2.2 特异性和敏感性 10

3.2.3 回收率 11

3.2.4 基质效应 12

3.2.5 准确度(RE)和精密度(RSD) 13

3.2.6 稳定性 14

3.2.7 大鼠药代动力学实验结果 15

3.3 药代动力学研究 15

第四章 结论 17

参考文献 18

致谢 21

第一章 文献综述

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