DETERMINATION OF CHLORPHENIRAMINE IN HUMAN BLOOD SERUM

人血清中氯苯那敏的测定

• 批准号: 5200875
• 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/5200875
• 关键词: analytical method; blood chemistry; chlorpheniramine; cyclodextrins; deuterium; fluorescence; formates; gas chromatography mass spectrometry; glycoproteins; 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.

低十亿分之一浓度的扑尔敏的测定 正在开发血清以支持一项临床研究 在 Paul Turkeltaub 医学博士的指导下进行 免疫生物化学、DAPP、CBER。 已评估的一项程序 并部分验证，涉及提取、浓缩和气体 色谱法。 通过选择性离子监测检测扑尔敏 m/e 203 处特征碎片离子的质谱分析。 提取效率和注射体积通过添加标准化 四氘化扑尔敏和类似 D4 的监测 m/e 207 处的碎片离子。开发一种替代方法，该方法将 允许扑尔敏拆分为其对映体 组件，正在进行中。 对映体拆分尚未完成 使用气相色谱手性柱获得。 基于 HPLC 柱 α-糖蛋白和β-环糊精固定相上有 提供对映体分辨率，但检测扑尔敏 紫外吸收法尚未达到 ppb 水平。 其他高效液相色谱 检测方法尚未被评估为提供必要的 敏感性。 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 检测可以为检测提供必要的灵敏度 扑尔敏在血清平衡水平，同时允许对映体 物种形成。