Urinary excretion studies of meldonium after multidose parenteral application
| Autor: | Nenad Dikic, Marija Anđelković, Guro Forsdahl, Tomas Geisendorfer, Veronika Jeitler, Biljana Jančić-Stojanović, Günter Gmeiner |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Clinical Biochemistry Pharmaceutical Science Urine Pharmacology Models Biological 01 natural sciences Analytical Chemistry 03 medical and health sciences 0302 clinical medicine Urinary excretion Pharmacokinetics Tandem Mass Spectrometry Drug Discovery Healthy volunteers medicine Humans Meldonium Spectroscopy Detection limit Chemistry 010401 analytical chemistry 030229 sport sciences Middle Aged 3. Good health 0104 chemical sciences Substance Abuse Detection Injections Intravenous Doping analysis Female Chromatography Liquid Half-Life Methylhydrazines medicine.drug |
| Zdroj: | Journal of Pharmaceutical and Biomedical Analysis |
| Popis: | Meldonium is a drug exhibiting cardioprotective and anti-ischemic effects. Due to its potential performance-enhancing benefit in sports, meldonium was added to the World Anti-Doping Agency list of prohibited substances in 2016. Since then, a high number of adverse analytical findings reported on meldonium has questioned meldonium`s detection time in urine. Hence, the objective of the current study was to characterize the pharmacokinetic urinary excretion pattern of meldonium when administered as multiple intravenous injections. Three injections of 250 mg meldonium were given over a time period of five days to six healthy volunteers and urine samples were collected for eight months after the last injection of the drug. For the quantification of meldonium in urine, a liquid chromatography-tandem mass spectrometry method was fully validated according to the World Anti-Doping Agency guidelines in terms of specificity, matrix interferences, intra- and inter-day precision, accuracy, carry-over, robustness, linearity, limit of detection, and limit of quantification. The assay was successfully applied to the pharmacokinetic study. A three-compartment model was found to best describe the pharmacokinetics of meldonium with average alpha, beta, and gamma half-lives of 1.4 h, 9.4 h, and 655 h, respectively. The detection time in urine varied between 94 and 162 days. |
| Databáze: | OpenAIRE |
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