In vitro and in vivo metabolism profiles of cathinone and pseudoephedrine: Discrimination between khat and pseudoephedrine uses

In the present study, the metabolism of khat (Catha edulis) and pseudoephedrine was compared with the aim of identifying objective criteria that could be used to discriminate between them for forensic and doping-control purposes. An in vitro study using human liver microsomes and an in vivo study using rat urine were performed under harmonized experimental conditions. Biological samples were analyzed by liquid chromatography-tandem mass spectrometry, and the resulting metabolism profiles were qualitatively and semi-quantitatively compared. Several metabolites of khat (or cathinone) and pseudoephedrine were common in both models, confirming that cathine alone cannot serve as a specific marker of khat use. Cathinone was also detected in pseudoephedrine-treated rat urine, although only at very low concentrations, while the unchanged parent compound remained the predominant urinary species in both dosing conditions. Thus, these findings indicate that interpretation must rely on the overall parent-metabolite pattern and support the use of urinary pseudoephedrine-to-cathinone concentration ratios as tentative criteria to discriminate between khat and pseudoephedrine use.