DETERMINATION OF THE ENANTIOMERS OF CITALOPRAM, ITS DEMETHYLATED AND PROPIONIC-ACID METABOLITES IN HUMAN PLASMA BY CHIRAL HPLC

A stereoselective HPLC assay has been developed to analyze the enantio mers of citalopram and of its three main metabolites in plasma after t heir separation on a Chiracel OD column. Using a fluorescence detector , the limit of quantification in plasma samples was 15, 4, 5, and 2 ng /ml for the enantiomers of citalopram (CIT), desmethylcitalopram(DCIT) , didesmethylcitalopram (DDCIT), and for the citalopram propionic acid derivative (CIT-PROP), respectively. Except for CIT, all metabolites were derivatized with achiral reagents. Identification of the enantiom ers was realized with an optical rotation detector which showed that t he enantiomers invert their rotation depending on the polarity and nat ure of the solvent. Under varying conditions, a racemization study has shown that the pure enantiomers of CIT and its demethylated metabolit es are configurationally stable. Preliminary results obtained with fiv e patients treated with CIT show a mean S/R ratio of 0.7 for both CIT and its active metabolite DCIT and of 3.6 for CIT-PROP in plasma. This suggests that the pharmacologically relevant (+)-(S)-isomers of CIT a nd DCIT could be preferentially and steroselectively metabolized to CI T-PROP (C) 1995 Wiley-Liss, Inc.