DETERMINATION OF CHLORPHENIRAMINE IN HUMAN BLOOD SERUM

扑热息痛中低百万分之几的测定 正在开发血清以支持即将进行的一项临床研究 在保罗·图克尔陶布的指导下进行，医学博士，实验室 过敏性产品，DBP，CBER。有一种程序，已经过评估 以及部分验证，包括提取、浓缩和气体 层析法。扑尔敏的选择性离子检测 监测m/e特征碎片离子的质谱学 203.萃取效率和进样量通过以下方法归一化 四氢扑热息痛的添加及监测 类似的D4碎片离子，m/e为207。开发一种替代方案 方法，这将允许将扑尔敏分解为其 对映体成分，正在进行中。对映体拆分有 用气相色谱手性柱得不到。高效液相色谱仪 基于α-糖蛋白和β-环糊精的固定色谱柱 相提供了对映体的拆分，但检测到 扑热息痛在ppb水平上还没有通过紫外线完成。 吸光度。其他高效液相检测方法还没有被评估为 提供必要的敏感度。前柱的工作正在进行中 与氯甲酸苄酯反应的衍生化方法， 手性高效液相色谱和荧光检测可能提供必要的 扑尔敏在血清平衡状态下检测的灵敏度 水平，同时允许对映体物种形成。

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.