Excretion of mephedrone and its phase I metabolites in urine after a controlled intranasal administration to healthy human volunteers

Mephedrone is a stimulant drug structurally related to cathinone. At present, there are no data available on the excretion profile of mephedrone and its metabolites in urine after controlled intranasal administration to human volunteers. In this study, six healthy male volunteers nasally insufflated 100 mg of pure mephedrone hydrochloride (Day 1). Urine was collected at different timepoints on Day 1 and then on Days 2, 3 and 30. Samples were analysed for the presence of mephedrone and its metabolites, namely, dihydro‐mephedrone, nor‐mephedrone (NOR), hydroxytolyl‐mephedrone, 4‐carboxy‐mephedrone (4‐carboxy) and dihydro‐nor‐mephedrone (DHNM), by a validated liquid chromatography‐tandem mass spectrometry method. All analytes were detected in urine, where 4‐carboxy (C(max) = 29.8 μg/ml) was the most abundant metabolite followed by NOR (C(max) = 377 ng/ml). DHNM was found at the lowest concentrations (C(max) = 93.1 ng/ml). Analytes exhibited a wide range of detection windows, but only 4‐carboxy and DHNM were detectable in all samples on Day 3, extending the detection time of mephedrone use. Moreover, mephedrone had a mean renal clearance of 108 ± 140 ml/min, and 1.3 ± 1.7% of unchanged parent drug was recovered in urine in the first 6 h post administration. It is hoped that this novel information will be useful in future studies involving mephedrone and other stimulant drugs.