ABSTRACT Selective androgen receptor modulators (SARMs) were developed to reproduce the anabolic effects of testosterone while sparing the prostate, and are marketed as a safer alternative to anabolic steroids. Tissue selectivity is reproducible in preclinical models but largely metabolic in origin and small in humans, and no SARM has been approved in more than 25 years. In randomised trials, lean body mass rises dose‐dependently by roughly 1–1.5 kg, with suppression of testosterone, sex hormone‐binding globulin and high‐density‐lipoprotein cholesterol and, with some compounds, reversible rises in aminotransferases, while physical function improves inconsistently. In one randomised‐response survey of male gym users, lifetime prevalence was about 2.7%. As used in practice, at higher doses, stacked and unmonitored, the dominant serious harm is a cholestatic drug‐induced liver injury, prolonged but usually reversible, with endocrine suppression. In almost all cases, the product was not analysed, so undeclared androgens cannot be excluded. Products sold as SARMs are frequently mislabelled: in one analysis only about half contained a SARM at all, many contained a different unapproved drug, and doses were often wrong. SARMs have been prohibited at all times since 2008. Adverse analytical findings rose from 15 in 2014 to 142 in 2019, then fluctuated (139 in 2023, 106 in 2024), a series shaped by testing volume and screening breadth as well as by use. Most follow deliberate purchase of products sold as SARMs. Findings attributed to contaminated ordinary supplements are documented on limited evidence. We set out the implications for doping control and counselling.
ABSTRACT Following the patent expiration of the originator darbepoetin alfa, three biosimilar products have been marketed in Japan; however, their detectability by current anti‐doping methods has not yet been verified. The present study assessed whether these biosimilars can be detected in human urine, serum, plasma, and dried blood spots (DBS) using the established initial testing procedure and confirmation analysis for erythropoietin‐receptor agonists. The originator product and three biosimilars (5 μg, i.v.) were administered to healthy male volunteers. Samples collected up to 72 h postdose were subjected to immunopurification followed by sodium N ‐lauroyl sarcosinate polyacrylamide‐gel electrophoresis (SAR‐PAGE) as the initial testing procedure. Confirmation was performed by SAR‐PAGE with double blotting for serum and plasma. DBS and urine samples were confirmed by SAR‐PAGE using an alternative antibody, and urine samples were further examined by liquid chromatography–tandem mass spectrometry (LC–MS/MS). SAR‐PAGE analysis of the pharmaceutical preparations revealed product‐specific electrophoretic profiles: two biosimilars migrated slightly above one originator product as diffused smears, whereas the third produced a sharp band comparable to that of another originator product. Similar profiles were observed in postdose samples from all biological matrices, and all biosimilars remained detectable in urine, serum, plasma, and DBS for at least 72 h. Although some biosimilars showed distinct SAR‐PAGE banding patterns, product attribution remained limited. LC–MS/MS confirmed administered darbepoetin alfa in the 24 h urine samples but did not detect analyte in lower concentration samples, indicating that its performance was concentration‐dependent. Accordingly, SAR‐PAGE should incorporate reference standards beyond the originator product, particularly those with different band morphologies.
ABSTRACT N ‐(2‐Methoxybenzyl)‐2‐(trimethoxyphenyl)ethanamines (TMPEA‐NBOMe series) constitute a relatively new group of synthetic compounds, some of which are known as psychotomimetics on the illicit drug market and are subject to legal control in many countries (e.g., N ‐(2‐methoxybenzyl)‐2‐(3,4,5‐trimethoxyphenyl)ethanamine, also known as Mescaline‐NBOMe). Like their 2,5‐dimethoxy analogues (25X‐NBOMe series), they act as agonists at 5‐HT 2A receptors and affect behavioral and cognitive functions, albeit to a lesser extent. When the relative arrangement of the three methoxy groups on the phenylethyl moiety is altered (positional isomers), compounds of the TMPEA‐NBOMe series may lack psychoactive effects and therefore possess a legal status. The present study explores the potential of chromatography and mass spectrometry to differentiate positional isomers of the TMPEA‐NBOMe series that differ in the location of the three methoxy groups on the phenylethyl moiety and that have different legal statuses. Differentiation of positional isomers by gas chromatography was achieved through the separation of their trifluoroacetyl derivatives on an HP‐5 type column under isothermal conditions (230°C). Retention indices were determined for both the underivatized TMPEA‐NBOMe isomers and their N ‐trifluoroacetyl derivatives, providing additional criteria for identification in GC analysis. It was found that these isomers could be distinguished by electron ionization mass spectrometry only when mass spectra were recorded for both the underivatized compounds and their N ‐trifluoroacetyl derivatives, since the spectra of the latter exhibited substantial differences depending on the position of the three methoxy groups. As an alternative, this study proposes a derivatization‐free approach using high‐performance liquid chromatography–tandem mass spectrometry.
ABSTRACT Chiral amphetamine analysis is performed in forensic toxicology to determine the nature of amphetamine intake (therapeutic or illicit). It is crucial to the correct interpretation of amphetamine‐positive hair samples in terms of abstinence control and therapy compliance, where hair analysis is used to evaluate the average amphetamine use over a period of several months. However, interpretative challenges arise when different medication intakes and/or illicit drug consumption events contribute to the hair analysis result. Therefore, a retrospective study of authentic casework was conducted (2017–2025, n = 340) to assess the performance of chiral amphetamine analysis in hair and to enhance the interpretation of its results. Two liquid chromatography tandem mass spectrometry (LC–MS/MS) based methods were used and compared, based on chiral derivatization (i.e., indirect method) or a chiral stationary phase (i.e., direct method). Chiral analysis results are expressed as enantiomeric fractions (EF) of ( S )‐amphetamine in hair. Chiral analysis results in hair were interpreted as in accordance with therapy compliance (e.g., Elvanse or Attentin) (EF ≥ 0.95, n = 284) or illicit amphetamine use (EF ≤ 0.55, n = 32). Between these proposed cut‐offs, the results were indicative of combined use of medical and illicit amphetamine or of therapeutic use of mixed amphetamine salts products (e.g., Adderall) (0.55 < EF < 0.95, n = 24). It was shown that segmented hair analysis can be beneficial for the interpretation of such indicative results. This retrospective study shows that chiral amphetamine analysis in hair confidently distinguishes between (sole) therapeutic and (sole) illicit amphetamine use and has established a decision model for the interpretation of EFs in hair for forensic casework.
