The prevalence of trimetazidine use in athletes in Poland: excretion study after oral drug administration

The identification of trimetazidine in urine samples might result from administration of the permitted drug lomerizine. Laboratories are therefore urged to carefully investigate suspicious cases where trimetazidine is detected. Differentiation of abuse of the banned substance trimetazidine from use of the permitted drug lomerizine would be supported by analysis of the intact drug lomerizine and/or specific metabolites. Copyright © 2015 John Wiley & Sons, Ltd.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analytical detection of trimetazidine produced by metabolic conversion of lomerizine in doping control analysis

Okano¹,

Thevis

Sato³

et al. 2015

“…Both assays proved fit‐for‐purpose with LODs concerning trimetazidine of 0.5 ng/mL respectively 14 ng/mL, and controlled elimination studies indicated detection windows of > 24 h after a single therapeutic dose of the coronary vasodilator. Until its inclusion in the list of prohibited substances in January 2014, the prevalence of trimetazidine use among athletes resulted in up to 39 identifications per year or 0.23% of findings …”

Section: Hormone and Metabolic Modulatorsmentioning

confidence: 99%

“…Until its inclusion in the list of prohibited substances in January 2014, the prevalence of trimetazidine use among athletes resulted in up to 39 identifications per year [180] or 0.23% of findings. [181] Diuretics and other masking agents Detecting diuretics in routine doping controls has been considerably simplified since LC-MS/MS analyses have become routinely available, and LODs for most diuretic agents have been reported in low ng/mL ranges over recent years. Besides facilitating initial testing protocols, the enhanced sensitivity resulted also in unusual findings such as the recently reported detection of chlorazanil in doping control samples.…”

Section: Hormone and Metabolic Modulatorsmentioning

confidence: 99%

Annual banned‐substance review: analytical approaches in human sports drug testing

Thevis

Kuuranne

Walpurgis

et al. 2016

The aim of improving anti-doping efforts is predicated on several different pillars, including, amongst others, optimized analytical methods. These commonly result from exploiting most recent developments in analytical instrumentation as well as research data on elite athletes' physiology in general, and pharmacology, metabolism, elimination, and downstream effects of prohibited substances and methods of doping, in particular. The need for frequent and adequate adaptations of sports drug testing procedures has been incessant, largely due to the uninterrupted emergence of new chemical entities but also due to the apparent use of established or even obsolete drugs for reasons other than therapeutic means, such as assumed beneficial effects on endurance, strength, and regeneration capacities. Continuing the series of annual banned-substance reviews, literature concerning human sports drug testing published between October 2014 and September 2015 is summarized and reviewed in reference to the content of the 2015 Prohibited List as issued by the World Anti-Doping Agency (WADA), with particular emphasis on analytical approaches and their contribution to enhanced doping controls.

“…13 Trimetazidine is generally identified by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS) 5,14 and gas chromatography-mass spectrometry (GC-MS). 15 The reported limits of detection (LODs) were 0.5 ng/mL for LC-MS/MS 14 and 5-50 ng/mL for GC-MS, 15 which could not properly evaluate the elimination phase in human excretion studies.…”

mentioning

confidence: 99%

Lomerizine, trimetazidine and bis‐(4‐fluorophenyl)‐methylpiperazine in human urine after oral administration of lomerizine dihydrochloride: analysis by liquid chromatography‐high resolution‐tandem mass spectrometry

Okano¹,

Sato²,

Kageyama³

2018

In sports drugs testing, the differentiation between the abuse of the prohibited substance trimetazidine and that of the permitted drug lomerizine is required because trimetazidine is one of the metabolites of lomerizine. Therefore, it is important to identify a lomerizine-specific metabolite in urine that allows making the distinction.In this study, a simple dilute-and-shoot method employing liquid chromatographyhigh resolution-tandem mass spectrometry for the quantification of trimetazidine, lomerizine and the specific metabolite bis-(4-fluorophenyl)-methylpiperazine (M6) in urine was developed. An oral dose of 15 mg was administered to 10 male volunteers, after which urine samples collected during the following 276 hours were analyzed using the developed method, allowing for examination of the target analytes' excretion profile. The limit of detection of all target analytes was <0.02 ng/mL. In all volunteers, the metabolite M6 was detected up to 276 hours after administration. After more than 12 hours, all volunteers were found to have higher concentrations of the metabolite M6 than of trimetazidine. The concentrations of trimetazidine, lomerizine, M6, and the M6/trimetazidine ratio in the final sample collected after 276 hours were 0.2-0.9 ng/mL, <0.05-0.1 ng/mL, 14.1-38.3 ng/mL, and 28.8-122.9, respectively.The urinary excretion of trimetazidine, unchanged lomerizine, and the metabolite M6 within the first 276 hours was 0.64%, 0.006%, and 6.1%, respectively. Consequently, the absence of the metabolite M6 in doping control urine samples corroborates the conclusion that lomerizine is unlikely to be the source of trimetazidine.The results confirm that the M6 metabolite is the longest-lasting urinary metabolite of lomerizine currently known.