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。 在保罗·图克尔陶布医学博士的指导下，过敏性产品 实验室，DBP，CBER。其中一个程序，已经过评估和 部分验证，包括提取、浓缩和气体 层析法。选择性离子监测法检测扑尔敏 M/e 203处特征碎片离子的质谱学。提取 效率和进样量通过添加 四氢扑尔敏及其类似物D4的监测 碎片离子的m/e为207。开发一种替代方法，那将是 允许将扑尔敏拆分成其对映体成分， 正在进行中。使用GAS尚未获得对映体拆分 色谱手性柱。基于α-糖蛋白的高效液相色谱柱 和β-环糊精固定相提供了对映体 分辨率，但尚未检测到ppb级别的扑尔敏 通过紫外线吸收来完成的。其他高效液相色谱检测方法还没有 被评估为提供了必要的敏感性。这项工作正在进行中 柱前衍生化方法，涉及与 氯甲酸苄酯、手性高效液相和荧光检测 为扑尔敏的检测提供必要的灵敏度 在允许对映体物种形成的同时，血清平衡水平。

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.