Determination of the antidepressant levoprotiline and its N-desmethyl metabolite in biological fluids by gas chromatography/mass spectrometry.

A specific and sensitive gas chromatographic/mass spectrometric method was developed and validated for the determination of the antidepressant levoprotiline in blood, plasma and urine and the simultaneous determination of levoprotiline and its desmethyl metabolite in urine. Deuterium-labelled analogues were used as internal standards. The compounds were isolated from the biological fluids by liquid-liquid extraction under basic conditions. Following derivatization with perfluoropropionic anhydride, the samples were analysed by capillary column gas chromatography/electron impact mass spectrometry with selected ion monitoring. The analysis of spiked samples demonstrated the high accuracy and precision of the method. Blood concentrations of levoprotiline down to 0.7 nmol l-1 (1 ml used for analysis) could be quantified with a coefficient of variation of 10% or less. The method is suitable for use in pharmacokinetic and bioavailability studies of levoprotiline in humans.