ABSTRACT
A high-performance liquid chromatographic method is used for the determination of citalopram [1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-5-phthalancarbonitrile+ ++] and four of its metabolites (the methylamino, amino, propionic acid and N-oxide derivatives) in plasma and urine. The plasma samples were extracted with diethyl ether at pH 10 and pH 4. Filtered urine samples could be injected directly on to the column. Steady-state drug and metabolite levels were investigated in fifteen psychiatric patients. In urine, 12 +/- 5% (mean +/- S.D.) of a given dose of citalopram was excreted in unchanged form. The propionic acid derivative was further conjugated, possibly to glucuronic acid. Mean steady-state plasma levels and metabolites in 24-h urine are given as percentages of the dose.
Subject(s)
Mental Disorders/metabolism , Propylamines/blood , Adult , Aged , Antidepressive Agents/blood , Antidepressive Agents/urine , Biotransformation , Chromatography, High Pressure Liquid/methods , Citalopram , Female , Humans , Male , Mass Spectrometry/methods , Mental Disorders/drug therapy , Middle Aged , Propylamines/therapeutic use , Propylamines/urine , Serotonin Antagonists/blood , Serotonin Antagonists/urine , Spectrometry, Fluorescence/methodsABSTRACT
A high-performance liquid chromatographic method is described for the determination of citalopram [1-(3-(dimethylaminopropyl)-1-(4-fluorophenyl)-5-phthalancarbonitrile] and its two main metabolites (the methylamino and amino derivatives). The compounds were extracted from alkaline plasma with diethyl ether. The combined ether layers were evaporated after addition of 50 microliter of 0.1 N HCl. The residual extracts were purified with diethyl ether and 20 microliter were injected into a Spherisorb ODS 5-micrometer column with acetonitrile--0.6% phosphate buffer pH 3 (55:45, v/v) as the mobile phase. Using a fluorescence detector the detection limits are 1 ng/ml of plasma for citalopram and the methylamino metabolite and 0.5 ng/ml for the amino metabolite.