Stereoselective determination of demethyl‐ and didemethyl‐citalopram in rat plasma and brain tissue by liquid chromatography with fluorescence detection using precolumn derivatization

A rapid and sensitive HPLC enantioselective method with fluorescence detection was developed to determine (−)‐( R ) and (+)‐( S ) enantiomers of the metabolites of citalopram, demethyl‐ and didemethyl‐citalopram in plasma and brain tissue. This assay involves pre‐column chiral derivatization with (−)‐( R )‐1‐(1‐naphthyl)ethyl isocyanate followed by separation on a normal‐phase silica column. The developed liquid–liquid extraction procedure permits quantitative determination of analytes with recoveries ranged between 81 and 88% with intra‐ and inter‐day relative standard deviations less than 10.5%. Linearity was obtained over the concentration range 5–1000 ng/mL and 100–10,000 ng/g for spiked drug‐free plasma and brain tissue, respectively, with detection limits lower than 2.1 ng/mL and 42.8 ng/g. Copyright © 2007 John Wiley & Sons, Ltd.