Gas chromatography-mass spectrometry detection of a norfluoxetine artifact in hydrolyzed urine samples may falsely indicate tranylcypromine ingestion

Abstract

In several cases, fluoxetine, its metabolites, its known artifacts, and supposedly tranylcypromine were detected in urine using the authors' systematic toxicological analysis (STA) procedure based on acid hydrolysis, extraction, and acetylation. As fluoxetine and tranylcypromine are absolutely contraindicated drugs and in none of the cases was tranylcypromine prescribed, the question of whether the detected compound might have been formed by fluoxetine and/or its metabolites arose. Therefore, rat urine taken after dosing with fluoxetine was screened in the same way. In addition, aqueous solutions of fluoxetine, norfluoxetine, tranylcypromine, and a mixture of the latter two drugs were worked-up and analyzed according to the STA and without hydrolysis. In urine specimens obtained from rats dosed with fluoxetine, tranylcypromine was detected as well as in the solution of worked-up norfluoxetine including hydrolysis. Its underlying mass spectrum could be identified by detailed interpretation of the fragmentation patterns as acetylated 3-phenyl-propyl-2-ene-amine. This compound could be postulated as hydrolysis product of norfluoxetine formed by ether cleavage and water elimination. Although this spectrum shows nearly the same fragmentation patterns as that of acetylated tranylcypromine, both compounds could finally be differentiated by their retention indices and by using the positive-ion chemical ionization mode.