DETERMINATION OF CHLORPHENIRAMINE IN HUMAN BLOOD SERUM

人血清中氯苯那敏的测定

• 批准号: 3748316
• 负责人: A V DEL GROSSO
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3748316
• 关键词: analytical method; blood chemistry; chlorpheniramine; deuterium; fluorescence; gas chromatography mass spectrometry; high performance liquid chromatography; human tissue; method development; stereoisomer

The determination of chlorpheniramine at low part per billion levels in blood serum is being developed to support a clinical study to be conducted under the direction of Paul Turkeltaub, M.D., Lab of Immunobiochemistry, DAPP, CBER. One procedure, that has been evaluated and partially validated, involves extraction, concentration and gas chromatography. Chlorpheniramine is detected by selective ion monitoring mass spectrometry of a characteristic fragment ion at m/e 203. Extraction efficiency and injection volume are normalized by addition of tetradeuterated chlorpheniramine and monitoring of the analogous D4 fragment ion at m/e 207. Development of an alternate method, that would permit the resolution of chlorpheniramine into its enantiometic components, is in progress. Enantiomeric resolution has not been obtained using gas chromatographic chiral columns. HPLC columns based on alpha-glycoprotein and beta-cyclodextrin stationary phases have provided enantiomeric resolution, but detection of chlorpheniramine at ppb levels has not been accomplished by UV absorbance. Other HPLC detection methods have not been evaluated as providing necessary sensitivity. Work is in progress on a pre- column derivatization method involving reaction with benzylchloroformate, chiral HPLC and fluorescence detection that may provide the necessary sensitivity for detection of chlorpheniramine at serum equilibrium levels while allowing enantiomeric speciation.

氯苯那敏的检测方法 正在开发血清以支持临床研究， 在Paul Turkeltaub，M.D.的指导下进行，实验室 免疫生物化学，DAPP，CBER。 一个程序，已经被评估 部分验证，涉及提取，浓缩和气体 层析 扑尔敏通过选择性离子监测检测 特征碎片离子的质谱，m/e 203。 提取效率和进样体积通过添加以下标准化： 四氘代氯苯那敏和类似物D4的监测 碎片离子m/e 207。 开发一种替代方法，这将 允许扑尔敏拆分成其对映体 组件，正在进行中。 对映异构体拆分尚未被 使用气相色谱手性柱获得。 基于HPLC色谱柱 在α-糖蛋白和β-环糊精固定相上， 提供了对映体的决议，但检测扑尔敏在 ppb水平尚未通过UV吸光度实现。 其他HPLC 检测方法尚未被评估为提供必要的 灵敏度 柱前衍生化方法的工作正在进行中 涉及与氯甲酸苄酯的反应、手性HPLC和荧光 可以提供必要的灵敏度，用于检测 扑尔敏在血清平衡水平，同时允许对映体 物种形成