DETERMINATION OF CHLORPHENIRAMINE IN HUMAN BLOOD SERUM

人血清中氯苯那敏的测定

• 批准号: 3792388
• 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/3792388
• 关键词: analytical method; chlorpheniramine; fluorescence; gas chromatography; high performance liquid chromatography; mass spectrometry; method development; serum; 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., Laboratory of Allergenic Products, 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.

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 过敏产品，DBP，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 扑尔敏采用选择性离子检测 在m/e处特征碎片离子的监测质谱法 203. 提取效率和进样体积通过下式标准化： 添加四氘代氯苯那敏并监测 类似的D4碎片离子，m/e 207。 开发替代品 方法，这将允许氯苯那敏到其分辨率 对映体组分，正在进行中。 对映体拆分具有 不能使用气相色谱手性柱获得。 HPLC 基于α-糖蛋白和β-环糊精固定相的色谱柱 相提供了对映体的分辨率，但检测 在ppb水平的扑尔敏还没有完成紫外线 吸光度 尚未评价其他HPLC检测方法， 提供必要的灵敏度。 一个前专栏的工作正在进行中 涉及与氯甲酸苄酯反应的衍生化方法， 手性HPLC和荧光检测，可以提供必要的 扑尔敏血清平衡检测灵敏度 水平，同时允许对映体物种形成。