论文总字数：14683字

摘 要

目的: 通过建立体内分析方法，测定比格犬血浆中双氯芬酸的浓度，研究双氯芬酸胶囊在比格犬体内的药代动力学。方法：高效液相色谱法。结果: 双氯芬酸的保留时间约为9min，内标保留时间约为3min，峰型、分离度均良好。双氯芬酸血药浓度与峰面积比值在0.1~7.5μg/mL范围内呈良好的线性关系，双氯芬酸血浆样品反复冻融3次稳定，并在处理后进样期间稳定。方法专属性研究、标曲线性范围、精密度试验、回收率试验及稳定性试验结果均达到要求。自制胶囊与原研胶囊的药时曲线较为相似。结论:血浆中内源性物质对药物含量测定无干扰。体内分析方法可行，自制胶囊与原研胶囊具有生物等效性。

关键词：双氯芬酸胶囊 药代动力学 高效液相色谱法

Study on internal pharmacokinetics of diclofenac capsules in Beagle Dog

ABSTRACT

OBJECTIVE：By establishing an in vivo analysis method，for the determination of the concentration of diclofenac in Beagle dog plasma and for the pharmacokinetic study of diclofenac in healthy female dogs． METHOD ： HPLC RESULTS ：The retention time of diclofenac was about 9min, the retention time of the internal standard is about 3min, and it has good peak shape and good separation.The ratio of diclofenac blood concentration and peak area showed a good linear relationship in the range of 0.1~7.5 g/mL,diclofenac plasma samples after 3 times of freeze thawing were stable, and after treatment they were stable during the sample period.The results of method specificity study、standard curve and linear range、precision test、recovery test and stability test all meet the requirements.The blood concentration time curve of the self-made capsule were similar with the original research capsule.CONCLUSION: Determination of drug content was not interfered by endogenous substance in plasma.The method of internal analysis is feasible, the original research capsule and the self-made capsule have the biological equivalence.

KEY WORDS: Diclofenac capsules; Pharmacokinetics; HPLC

目 录

摘要 I

ABSTRACT II

第一章 文献调研 1

1.1 研究背景 1

1.2 双氯芬酸简介 1

1.2.1 药物简介 1

1.2.2 药物基本信息 1

1.2.3 药理原理 2

1.3 实施方案与设计方法 2

1.3.1 文献查阅 2

1.3.2 开展实验研究 2

1.3.3 一般动物实验的给药方法与剂量控制 3

1.4 本课题主要研究内容 3

第二章 实验部分 4

2.1 材料与仪器 4

2.1.1 实验试剂 4

2.1.2 实验仪器 4

2.1.3 受试动物 4

2.2 体内分析法的建立......................................................................4

2.2.1 色谱条件 4

2.2.2 血浆样品处理 5

2.2.3 方法专属性研究 5

2.2.4 标准曲线的制备 5

2.2.5 精密度试验 5

2.2.6 回收率试验 5

2.2.7 稳定性试验 6

2.3 动物体内实验 6

2.3.1 给药剂量的换算 6

2.3.2 单剂量口服给药方案 6

2.4 数据处理和统计分析 7

第三章 实验结果 8

3.1方法专属性研究 8

3.2 标准曲线与线性范围 9

3.3 精密度 9

3.4 回收率试验 10

3.5 稳定性试验 11

3.6 动物体内试验结果 12

3.6.1 比格犬体内药代动力学 12

第四章 全文总结 13

参考文献 14

致谢 16

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