DETERMINATION OF CHLORPHENIRAMINE IN HUMAN BLOOD SERUM

扑热息痛中低百万分之几的测定 目前正在开发血清以支持即将进行的临床研究。 在免疫生物化学实验室医学博士保罗·特克尔陶布的指导下， DAPP，CBER。其中一个程序已经过评估和部分验证， 包括萃取、浓缩和气相色谱。 选择性离子监测质谱法测定扑尔敏 在m/e 203处的特征碎片离子。萃取效率和 通过加入四氢化氢使注射体积归一化 扑尔敏及其类似D4碎片离子的m/e监测 207.开发一种替代方法，这将允许决议 将扑尔敏转化为对映体成分的工作正在进行中。 用气相色谱尚未获得对映体的拆分 手性柱。基于α-糖蛋白和α-糖蛋白的高效液相色谱法 β-环糊精固定相提供了对映体拆分， 但是扑尔敏在ppb水平上的检测还没有完成。 通过紫外线吸收。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 与手性氯甲酸苄酯反应的衍生化方法 高效液相色谱和荧光检测，可提供必要的灵敏度 用于检测扑热息痛在血清平衡水平，而 允许形成对映体物种。

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.