The possibility of nutritional supplement contamination with minute amounts of the selective androgen receptor modulator (SARM) ostarine has become a major concern for athletes and result managing authorities. In case of an adverse analytical finding (AAF), affected athletes need to provide conclusive information, demonstrating that the test result originates from a contamination scenario rather than doping. The aim of this research project was to study the elimination profiles of microdosed ostarine and characterize the time‐dependent urinary excretion of the drug and selected metabolites. Single‐ and multi‐dose administration studies with 1, 10, and 50 μg of ostarine were conducted, and collected urine samples were analyzed by LC‐MS/MS following solid‐phase extraction or enzymatic hydrolysis combined with liquid‐liquid extraction.
In the post‐administration samples, both the maximum urine concentrations/abundance ratios and detection times of ostarine and its phase‐I and phase‐II metabolites were found to correlate with the administered drug dose. With regard to the observed maximum levels of ostarine, the time points of peak urinary concentrations/abundance ratios, and detection windows, a high inter‐individual variation was observed. However, the study demonstrated that a single oral dose of as little as 1 μg can be detected for up to 9 (5) days by monitoring ostarine (glucuronide), and hydroxylated metabolites (especially M1a) appear to offer a considerably shorter detection window.
The obtained data on ostarine (metabolite) detection times and urinary concentrations following different administration schemes support the interpretation of AAFs, in particular when scenarios of proven supplement contamination are discussed and supplement administration protocols exist.
Rationale:
Chlorphenesin is an approved biocide frequently used in cosmetics, and its carbamate ester is an approved skeletal muscle relaxant in certain countries for the treatment of discomfort related to skeletal muscle trauma and inflammation. A major urinary metabolite is 4‐chlorophenoxy acetic acid (4‐CPA), also known as para‐chlorophenoxyacetate, which is also employed as a target analyte in sports drug testing to detect the use of the prohibited nootropic stimulant meclofenoxate. To distinguish between 4‐CPA resulting from chlorphenesin, chlorphenesin carbamate, and meclofenoxate, urinary metabolite profiles of chlorphenesin after legitimate use were investigated.
Methods:
Human administration studies with commercially available sunscreen containing 0.25% by weight of chlorphenesin were conducted. Six study participants dermally applied 8 g of sunscreen and collected urine samples before and up to 7 days after application. Another set of six study participants applied 8 g of sunscreen on three consecutive days, and urine samples were also taken for up to 5 days after the last dosing. Urine specimens were analyzed using liquid chromatography‐high resolution (tandem) mass spectrometry, and urinary metabolites were identified in accordance with literature data by accurate mass analysis of respective precursor and characteristic product ions.
Results:
In accordance with literature data, chlorphenesin yielded the characteristic urinary metabolites, chlorphenesin glucuronide, chlorphenesin sulfate, and 3‐(4‐chlorophenoxy)‐2‐hydroxypropanoic acid (4‐CPP), as well as the common metabolite 4‐CPA. 4‐CPA and 4‐CPP were observed at similar abundances, with urinary concentrations of 4‐CPA reaching up to ~1500 and 2300 ng/mL after single and multiple sunscreen applications, respectively.
Conclusion:
4‐CPA is a common metabolite of meclofenoxate, chlorphenesin, and chlorphenesin carbamate. Monitoring the diagnostic urinary metabolites of chlorphenesin provides conclusive supporting evidence of whether chlorphenesin or the prohibited nootropic meclofenoxate was administered.
Serological test methods to detect anti-SARS-CoV-2 antibodies represent a major measure to manage the pandemic caused by the coronavirus disease 2019 . In this communication, test results obtained from minimal-invasively collected dried blood spot (DBS) specimens, which can be sampled 'at home' without the need of medically trained personnel, are compared to conventionally collected venous blood samples. DBS samples were prepared for analysis either manually or by a card extraction robot, and electrochemiluminescence assay (ECLIA) characteristics, assay readout values as well as stability data covering a period of more than 200 days are provided. Constant anti-SARS-CoV-2 antibody readouts of quality control DBS were obtained over the entire test period using DBS specimens stored under dry and dark conditions. In addition, test results obtained from individuals tested twice within 10 months post-infection indicated a consistent presence of antibodies.
Higenamine is prohibited in sports as a β2‐agonist by the World Anti‐Doping Agency. As a key component of a great variety of plants, including the Annonaceae family, one aim of this research project was to evaluate whether the ingestion of Annona fruit could lead to higenamine adverse analytical findings. Single‐dose administration studies including three Annona species (i.e., Annona muricata, Annona cherimola, and Annona squamosa) were conducted, leading to higenamine findings below the established minimum reporting level (MRL) of 10 ng/mL in urine. In consideration of cmax values (7.8 ng/mL) observed for higenamine up to 24 h, a multidose administration study was also conducted, indicating cumulative effects, which can increase the risk of exceeding the applicable MRL doping after Annona fruit ingestion. In this study, however, the MRL was not exceeded at any time point. Further, the major urinary excretion of higenamine in its sulfo‐conjugated form was corroborated, its stability in urine was assessed, and in the absence of reference material, higenamine sulfo‐conjugates were synthesized and comprehensively characterized, suggesting the predominant presence of higenamine 7‐sulfate. In addition, the option to include complementary biomarkers of diet‐related higenamine intake into routine doping controls was investigated. A characteristic urinary pattern attributed to isococlaurine, reticuline, and a yet not fully characterized bismethylated higenamine glucuronide was observed after Annona ingestion but not after supplement use, providing a promising dataset of urinary biomarkers, which supports the discrimination between different sources of urinary higenamine detected in sports drug testing programs.
INTRODUCCIÓN: presentamos la primera Clínica de anticoagulación perteneciente al sector de salud pública en Bogotá, que forma parte de la Red Distrital de Salud, la cual está adscrita a la Subred integrada de servicios de salud Centro Oriente, de la Secretaría Distrital de Salud de Bogotá.
METODOLOGÍA: se trata de un estudio descriptivo retrospectivo que muestra los resultados de la terapia anticoagulante con warfarina, heparinas de bajo peso molecular y los nuevos anticoagulantes inhibidores directos; también se describe la adherencia, los efectos adversos y las complicaciones con esta terapia, el tiempo dentro del rango terapéutico y otros hallazgos obtenidos del análisis retrospectivo del grupo de pacientes estudiados, los cuales son muy similares a los reportados por otras clínicas de anticoagulación en la literatura.
CONCLUSIONES: se evidencia la importancia de la implementación de estas clínicas para obtener un manejo óptimo de los pacientes con indicación de anticoagulación.
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