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. 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. HPLC columns based on alpha-glycoprotein and beta-cyclodextrin stationary phases have provided enantiomeric resolution. 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.