DETERMINATION OF CHLORPHENIRAMINE IN HUMAN BLOOD SERUM

人血清中氯苯那敏的测定

• 批准号: 3804668
• 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/3804668
• 关键词: analytical chemistry; blood; chlorpheniramine; fluorescence; gas chromatography; high performance liquid chromatography; human tissue; mass spectrometry; serum; technology /technique development

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., Allergenic Products laboratory, DBP, 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 enantiomeric 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即将进行的临床研究 在过敏产品医学博士 Paul Turkeltaub 的指导下 实验室、DBP、CBER。 一项程序，已被评估并 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。萃取 效率和注射量通过添加标准化 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 允许扑尔敏拆分成其对映体成分， 正在进行中。 尚未使用气体实现对映体拆分 色谱手性柱。 基于 α-糖蛋白的 HPLC 柱 和β-环糊精固定相提供了对映体 分辨率，但尚未检测到 ppb 水平的扑尔敏 通过紫外吸收来完成。 其他HPLC检测方法尚未被采用 评估为提供必要的灵敏度。 工作正在进行中 柱前衍生化方法涉及与 氯甲酸苄酯、手性 HPLC 和荧光检测可能 为扑尔敏的检测提供必要的灵敏度 血清平衡水平，同时允许对映体形态。