Lomerizine M6—An Important Urinary Metabolite in Anti‐Doping Control Analysis for Correct Detection of Trimetazidine Abuse in Both Females and Males

Distinguishing between intake of the prohibited substance trimetazidine from administration of approved migraine medicine containing the nonprohibited substance, lomerizine, is crucial for anti-doping control laboratories. Investigations in males after lomerizine intake have been conducted leaving lomerizine M6 as the most useful metabolite. To our knowledge, the excretion profile of lomerizine among women has not been studied and leaves a potential gap to be misused by athletes in the case of appeal of a reported adverse analytical finding. We have investigated lomerizine M6 in women to address the gender-specific biology to correctly detect misusage of the prohibited substance trimetazidine within sports. To determine the importance of lomerizine M6 in trimetazidine cases, we analyzed urine samples collected from 12 individuals (eight females and four males) over 144 h, after oral intake of 5-mg lomerizine dihydrochloride. A dilute and shoot method was used, and the samples were analyzed on a LC-HRMS instrument. In all study subjects, trimetazidine was found from 2 h up to 48 h, and lomerizine M6 was detected from 2 h and onward. Lomerizine was only detected above the limit of identification of the method for a few of the subjects. The study demonstrated that by monitoring lomerizine M6, it was possible to determine the origin of trimetazidine in women. The metabolism for lomerizine dihydrochloride does not appear to differ significantly between genders. However, lomerizine M6 concentrations are not always higher than trimetazidine concentrations. Special care should be taken when interpreting trimetazidine concentrations at 1 ng/mL or below.