Figure - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Scheme 4. Proposed dissociation pathway of the deprotonated metabolite M3. Scheme 4. Proposed dissociation pathway of the deprotonated metabolite M3.
Source publication
Among anabolic agents, selective androgen receptor modulators (SARMs) represent a new class of potential drugs that can exhibit anabolic effects on muscle and bone with reduced side effects due to a tissue-selective mode of action. Besides possible medical applications, SARMs are used as performance-enhancing agents in sports. Therefore, they are p...
Context in source publication
Citations
... Among them, studies with subcellular fractions, such as microsomes and the S9 fraction, usually provide a high number of metabolites and are useful to quickly generate many potential metabolites and obtain retention times (RTs) and mass spectra to be matched with in vivo samples. Combined with advanced analytical techniques, especially UHPLC-HRMS-based approaches, remarkable progress has been made in the investigation of doping metabolism based on in vitro experiments [12,13]. However, some issues remain challenging. ...
Traditional strategies for the metabolic profiling of doping are limited by the unpredictable metabolic pathways and the numerous proportions of background and chemical noise that lead to inadequate metabolism knowledge, thereby affecting the selection of optimal detection targets. Thus, a stable isotope labeling-based nontargeted strategy combined with ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS) was first proposed for the effective and rapid metabolism analysis of small-molecule doping agents and demonstrated via its application to a novel doping BPC-157. Using 13C/15N-labeled BPC-157, a complete workflow including automatic 13C0,15N0-13C6,15N2 m/z pair picking based on the characteristic behaviors of isotope pairs was constructed, and one metabolite produced by a novel metabolic pathway plus eight metabolites produced by the conventional amide-bond breaking metabolic pathway were successfully discovered from two incubation models. Furthermore, a specific method for the detection of BPC-157 and the five main metabolites in human urine was developed and validated with satisfactory detection limits (0.01~0.11 ng/mL) and excellent quantitative ability (linearity: 0.02~50 ng/mL with R2 > 0.999; relative error (RE)% < 10% and relative standard deviation (RSD)% < 5%; recovery > 90%). The novel metabolic pathway and the in vitro metabolic profile could provide new insights into the biotransformation of BPC-157 and improved targets for doping control.
Selective androgen receptor modulators (SARMs) are performance‐enhancing drugs (PEDs) that stimulate anabolism, increase muscle mass and strength and promote recovery from exercise. The use of SARMs in sports is considered doping and is strictly prohibited by the World Anti‐Doping Agency (WADA) and the International Federation of Horseracing Authorities (IFHA). To monitor the abuse of SARMs in sports, it is essential to develop advanced, selective and sensitive analytical methods that provide reliable results. This review evaluates the advances in this area, with a focus on the identification of target analytes related to SARMs, such as SARMs, their metabolites or markers. The aim is to identify targets that could extend the detection windows of SARMs, provide scientific support for results management and/or offer an indirect biomarker‐based approach to doping control. This review also aims to evaluate the current liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) methods developed for the monitoring of SARMs in different biological matrices, including traditional matrices such as urine and serum/plasma samples, as well as alternative matrices such as dried blood spots, hair and nail samples.
In this 16 th edition of the annual banned‐substance review on analytical approaches in human sports drug testing, literature on recent developments in this particular section of global anti‐doping efforts that was published between October 2022 and September 2023 is summarized and discussed. Most recent additions to the continuously growing portfolio of doping control analytical approaches and investigations into analytical challenges in the context of adverse analytical findings are presented, taking into account existing as well as emerging challenges in anti‐doping, with specific focus on substances and methods of doping recognized in the World Anti‐Doping Agency's 2023 Prohibited List. As in previous years, focus is put particularly on new or enhanced analytical options in human doping controls, appreciating the exigence and core mission of anti‐doping and, equally, the conflict arising from the opposingly trending extent of the athlete's exposome and the sensitivity of instruments nowadays commonly available in anti‐doping laboratories.
