Meldonium determination in milk and meat through UHPLC-HRMS

Abstract

A simple and sensitive procedure for the quantification of meldonium in milk and meat by UHPLC-HRMS is presented. Some products were investigated to contain this substance due to using a veterinary drug called “Emidonol”. According to the instruction for this drug, it can be used for injection (for cows) and as an additive in drinking water for chickens. Although meldonium is not a threat for human health, it is strictly prohibited in professional sports according to WADA Prohibited List. Sample preparation conditions were optimized for both matrices that allowed to eliminate matrix effects and achieve reproducible and accurate results. Protein precipitation with dilution were applied for milk samples, while chicken meat and liver were homogenized with quartz sand to achieve satisfactory meldonium recovery. The results of milk and meat samples analysis purchased at the farmers’ fair are presented in this article. Meldonium concentration in raw milk was investigated to be up to 880 ng/mL. However, pasteurization can be used for partial cleanup from meldonium (up to 2 times). The same research was conducted for chicken meat and liver. Thermal treatment shows a good result for a meat cleanup. The proposed method was partially validated, limits of detection and quantification were established for each matrix.

Sports drug testing and the athletes' exposome

“…In consideration of that aspect, a urinary reporting level of 5 ng/ml was established, which is not expected to be exceeded through the ingestion of contaminated meat, based on drug residue levels known and reported by foodstuff inspections to date 43 . In a recent report, meldonium residues detected in milk and meat of meldonium‐treated cows and chicken were described 44 . The determined amounts appear to represent a significant risk for athletes to unknowingly ingest meldonium at levels that are traceable in doping control urine samples and, further, could potentially exceed the currently enforced urinary reporting level of 100 ng/ml 45,46 in selected regions where meldonium is approved for animal treatment and in farming.…”

Meldoniumas Kardiovaskulinių Ir Neurologinių Ligų Bei Cukrinio Diabeto Gydymui

“…A. Temerdashev ir kt. atliktas tyrimas parodė, kad ši veiklioji medžiaga linkusi akumuliuotis Emidonol preparatais gydytų karvių piene, viščiukų mėsoje ir kepenyse [8]. Ištirta, jog meldoniumo pėdsakai karvės piene gali būti aptinkami ir praėjus kelioms dienoms po paskutinės 10 d. trukmės (6 d. kasdienės injekcijos, po kurių 4 d. negydoma) gydymo kurso dienos, kartu įvertinta, kad terminis pieno apdorojimas meldoniumo koncentraciją sumažina tik iki dviejų kartų.…”

Meldonium residues in milk: A possible scenario for inadvertent doping in sports?

“…[6][7][8] Lately, the veterinary drug Emidonol ® (3-[2,2,2-trimethylhydrazinium]propionate-2-ethyl-6-methyl-3-hydroxypyridine disuccinate, Figure 1) has been discussed as a possible scenario for inadvertent doping in connection with meldonium. 9 According to its antihypoxic and weak sedative effects, Emidonol ® is used in livestock breeding, for example, for the treatment of cows via injection or chicken as a drinking water additive. In animals, the drug complex is rapidly metabolized to meldonium which is then excreted in its unchanged form.…”

“…In a recent study, meldonium concentrations determined in raw milk were up to 701 ng/ml, in chicken meat 260 ng/g, and in chicken liver 995 ng/g. 9 To investigate if contaminated food can possibly result in AAFs in doping controls, a pilot study was conducted with three volunteers consuming a single dose of 100 ml milk containing meldonium at a concentration of 500 ng/ml (50 μg absolute) and multiple doses of 100 ml of meldonium-containing milk (500 ng/ml) at five consecutive days. All samples were prepared using an established and validated protocol based on HILIC-HRMS published earlier.…”