论文总字数：21471字

摘 要

Abstract: 4

引言 5

1.研究背景 5

2.右兰索拉唑（RLSP）概述 5

2.1理化性质 5

2.2作用机理 6

2.3药理作用 6

2.4药物代谢动力学 6

2.5不良反应 6

3.LC-MS-MS技术概述 7

4.课题研究意义 7

实验内容 8

1.材料与设备 8

1.1基质 8

1.2试剂 8

1.3溶液 8

1.4实验器材及仪器 8

2.分析条件 9

2.1液相色谱条件 9

2.2质谱条件 9

3.溶液配制 9

3.1储备液配制 9

3.2工作液配制 10

3.3储备液检查 11

3.4标准曲线样品配制 11

3.5质控样品配制 11

4.样品前处理 11

5.方法学验证 12

5.1标曲的建立 12

5.2准确度、精密度 12

5.3进样残留 13

5.4专属性评价 13

5.5高脂基质评价 17

5.6回收率 18

5.7稀释准确性 20

5.8溶液稳定性 20

5.9基质稳定性 24

参考文献 28

致谢 30

摘要：目的：设计建立液相色谱-串联质谱法（LC-MS-MS）测定人血浆中右旋兰索拉唑（R-Lansoprazole）的含量。方法：以埃索美拉唑为内标，乙腈为蛋白沉淀剂。色谱条件：使用Daicel CHIRALPAK® IC 手性柱（4.60 mm×150mm,5.0 μm，Part No:83324）进行分离，预柱为Daicel CHIRALPAK® IC 手性预柱（4.60 mm×10.0 mm,5.0 μm，Part No: 83311），柱温25℃，以A相：乙腈：水 (95:5,v/v)，B相：5mM 醋酸铵0.05%乙酸溶液：乙腈（60:40, v/v）为流动相，流速为0.800ml/min。质谱条件：通过气动辅助电喷雾离子化(ESI), 以多重反应监测 (MRM) 模式进行正离子（Positive）检测, 右旋兰索拉唑、埃索美拉唑的MRM 离子对分别为m/z370.2→252.0、m/z346.2→198.2。结果：人血浆中右旋兰索拉唑在5.000～5000ng/ml浓度内线性关系良好(rgt;0.99),定量下限为5.000ng/ml；定量下限和质控样品的批内、批间精密度(%RSD)在2.56%～12.09%之间,准确度(RE%)在±15.00%以内；提取回收率及内标回收率%RSD均在15.0%以内。结论：可用于人血浆中的右旋兰索拉唑含量的测定。

关键词：右旋兰索拉唑，液相色谱-串联质谱法，血药浓度检测

Abstract: Objective: To design and establish a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the determination of R-Lansoprazole in human plasma.Methods: Esomeprazole was used as internal standard and acetonitrile as protein precipitant.Chromatographic conditions: Daicel CHIRALPAK® IC Chiral Precolumn (4.60 mm×150mm,5.0 μm, Part No:83324) was used for separation. The precolumn wasDaicel CHIRALPAK® IC Chiral Precolumn (4.60 mm×10.0 mm,5.0 μm, Part No: 83311), and the column temperature was 25℃. Phase A: acetonitrile: water (95:5,v/v), phase B: 5mM ammonium acetate 0.05% acetic acid solution: acetonitrile (60:40, v/v) was used as mobile phase with a flow rate of 0.800ml/min. Mass spectrometry conditions: Positive detection is performed in multiple reaction monitoring (MRM) mode through pneumatic assisted electrospray ionization (ESI). MRM ions of dexlansoprazole and esomeprazole are m/z370.2→252.0 and m/z346.2→198.2 respectively. Results: the linear relationship between the concentration of dexlansoprazole in human plasma was good (rgt;0.99) and the lower limit of quantification was 5.000ng/ml; The precision (%RSD) of the lower limit of quantification and quality control samples within and between batches is between 2.56% ~ 12.09%, and the accuracy (RE%) is within 15.00%. The recovery rate of extraction and internal standard were both within 15.0%RSD. Conclusion: This method is simple and effective, and can be used for the determination of dexlansoprazole in human plasma.

Key words: R-Lansoprazole, LC-MS-MS, Monitoring of blood drug concentration

引言

1.研究背景

社会的持续发展改善了人们的日常生活水平，但同时，人们也有了更大的压力，因为抽烟、喝酒、作息等因素的诱导，人们患上消化系统疾病的概率越来越大。我国一直是胃肠疾病高发国家，目前的发病率高达11.41%，而其中溃疡类发生率达到了4.51%[1]。

右旋兰索拉唑（R-Lansoprazole）是一种用于治疗食管炎的新型药物，由日本武田药业在二零零九年一月三十日经美国食品药物管理局批准后上市[2]。主要用于非糜烂性胃部灼热以及各个阶段的糜烂性食管炎[3]。临床Ⅲ期试验结果表明，本药的抑制胃酸分泌作用可长达二十四小时，并能有效持续缓解胃灼热及胃食管反流症状[4]。

2.右兰索拉唑（RLSP）概述

2.1理化性质

右旋兰索拉唑，分子式为C₁₆H₁₄F₃N₃O₂S,分子量为369.36。

化学结构式见图1-1。

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