Determination of Citalopram and its Main Metabolite Desmethylcitalopram in Human Serum by Column-Switching High Performance-Liquid Chromatography (HPLC) and Spectrophotometric Detection

Citalopram is the most frequently prescribed selective serotonin reuptake-inhibitor (SSRI) in psychiatric hospitals of the Arbeitsgemeinschaft Arzneimitteltherapie bei psychiatrischen Erkrankungen (AGATE) for depressive and panic disorders with and without agoraphobia. Effective daily doses are 20–40mg. Dopaminergic, adrenergic and GABA effects are minimal. Anticholinergic and antihistaminergic effects, typical side effects known from tricyclic antidepressants, are lacking.

Monitoring plasma concentrations of citalopram and its main metabolite desmethylcitalopram may be useful to improve the therapeutic effectiveness and minimize side effects and to reveal non-compliance.

We established a new method for quantitative and automated analysis of citalopram and desmethylcitalopram in serum using HPLC with column-switching. For sample clean-up serum was injected onto a pre-column to remove interfering proteins and lipids using LiChrospher CN 20µm, 10×2,1mm column and acetonitrile 8% in water as pre-column eluent. Drugs were eluted by back-flush flow onto the analytical column (LiChrospher CN 5µm, 250×4,6mm) at a flow rate of 1,5 mL/min with phosphate buffer 0,008 mol/l, pH6,4/acetonitrile (50/50; v/v). Haloperidol was used as an internal standard. Analytes were detected by ultraviolet spectrometry at 210 nm. Retention times were 21.7min for citalopram and 20.1min for desmethylcitalopram. The analytical run could be completed within 30min. The detection limit was 5 ng/ml, recoveries ranged from 62 to 88% for citalopram and from 56 to 89% for desmethylcitalopram.

The method was found to be suitable for automated analysis of serum samples of patients treated with citalopram for therapeutic drug monitoring or for pharmacokinetic studies.