{"title":"Performance-enhancing substances in sport: A scientometric review of 75 years of research.","authors":"Alessandro Carollo, Ornella Corazza, Maria Mantovani, Nicolò Silvestrini, Olivier Rabin, Gianluca Esposito","doi":"10.1002/dta.3677","DOIUrl":"10.1002/dta.3677","url":null,"abstract":"<p><p>The use of performance-enhancing substances not only undermines the core values of sports but also poses significant health risks to athletes. In a fast-evolving doping environment, where sport professionals are constantly seeking novel and illegal means to bypass doping tests, and new substances are regularly detected on the drug market, it is crucial to inform authorities with updated evidence emerging from scientific research. The current study aims to (i) outline the structure of knowledge in the literature on performance enhancers in sports (i.e., most active countries, main sources, most productive authors, and most frequently used keywords); (ii) identify the most impactful documents in the field; and (iii) uncover the main domains of research in the literature. To do so, we conducted a comprehensive scientometric analysis of the literature on doping, sourcing our data from Scopus. Our research involved a document co-citation analysis of 193,076 references, leading to the identification of the 51 most influential documents and seven key thematic areas within the doping literature. Our results indicate that the scientific community has extensively studied the most prevalent doping classes, such as anabolic agents and peptide hormones, and little is still known about the use of contaminated supplements or other types of enhancers identified as emergent trends. Concurrently, technological advancements contributed to the development of more sophisticated doping detection techniques, using blood or urine samples. More recently, the focus has shifted towards the athlete biological passport, with research efforts aimed at identifying biomarkers indicative of doping. The dynamic nature of doping methods underlines the necessity for more robust educational campaigns, aiming at raising awareness among sports professionals and their entourage about the dangers of doping and the intricacies of its control mechanisms.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":"13-24"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher Wiedfeld, Gisela Skopp, Frank Musshoff
{"title":"Single hair analysis for gamma-hydroxybutyric acid-Method optimization, validation, and application.","authors":"Christopher Wiedfeld, Gisela Skopp, Frank Musshoff","doi":"10.1002/dta.3683","DOIUrl":"10.1002/dta.3683","url":null,"abstract":"<p><p>As gamma-hydroxybutyric acid (GHB) underlies fast metabolization, its determination from hair may presumably offer a detection window superior to that of body fluids. Due to the wide range of endogenous concentration levels, the evidence of an exogenous ingestion is challenging. As already shown for other drugs, the temporal resolution obtained by applying single hair microanalysis provides further information. Therefore, a method for the extraction and quantification of GHB in 2-mm hair segments (seg) was optimized and validated (limit of detection [LOD]: 2.5 pg/seg, lower limit of quantification [LLOQ]: 5 pg/seg), and five single hairs were examined, each for three non-users and for three (alleged) users. A major challenge was the choice of appropriate extraction tubes without remains of GHB. In two samples from non-users, GHB could not or could only be detected in trace amounts. In the third sample, concentrations between the LOD and 31.1 pg/seg (mean: 9.5, median: 8.4; each pg/seg) were detected with decreasing values towards the tips. In two samples of persons with assumed GHB intake, maximum concentrations of 6.8 and 30.7 pg/seg were measured, but no significant concentration peaks indicating a single ingestion could be observed. The third sample showed concentrations of 7.6-55.2 pg/seg (mean: 28.8, median: 29.6; each pg/seg). In this case, the obtained profiles showing at least two reproducible concentration maxima between 20 and 40 mm point to an ingestion of GHB. The concentration profiles from single hairs were reproducible in each case, reflecting the concentration course of routine 1-cm segmental analysis. These are the first results published on GHB testing in segmented single hairs, and the results must be verified further.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":"25-33"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Infant exposure to drugs of abuse investigated by hair analysis.","authors":"Cestonaro Clara, Terranova Claudio, Cinquetti Alessandro, Russo Alessia, Aprile Anna, Favretto Donata","doi":"10.1002/dta.3674","DOIUrl":"10.1002/dta.3674","url":null,"abstract":"<p><p>Infant exposure to drugs of abuse represents a worldwide problem whose extent is difficult to estimate. Despite the potentially serious health consequences, few data concerning exposure in children under 1 year of age are available. Since in clinical and forensic settings, neonatal and infant hair testing represents a useful method for investigating suspected drug exposures, an observational retrospective study was performed on hair analysis of children under 1 year of age evaluated at the University Hospital of Padova between 2018 and 2022 with the aim of estimate the extent and define the characteristics of this phenomenon in the reference setting. The sample included 102 infants. Chemical-toxicological analyses were requested in 38 cases (37.3%) because of clinically suspicious symptoms of the child (e.g., neuropsychiatric symptoms and suspected neonatal abstinence syndrome) and in 64 cases (62.7%) because of other reasons (e.g., maternal drug history, at-risk environment, and suspected maltreatment). Based on the presence or absence of symptoms in the request, the sample was subdivided into two groups. Hair analysis in these two showed the presence of drug of abuse, respectively, in 44.7% and 67.2% of the cases (p = 0.026). Cocaine was the most frequently detected substance, followed by opiates, and it was detected less frequently in cases investigated for suspicious clinical symptoms (p < 0.05). The results confirm the difficulties in interpreting the clinical picture and in defining the extent of exposure to drugs of abuse. An integrated assessment is fundamental to interpret the case and achieve adequate care of the child.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":"7-12"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Annual Banned-Substance Review 17th Edition-Analytical Approaches in Human Sports Drug Testing 2023/2024.","authors":"Mario Thevis, Tiia Kuuranne, Hans Geyer","doi":"10.1002/dta.3835","DOIUrl":"https://doi.org/10.1002/dta.3835","url":null,"abstract":"<p><p>The 17th edition of the annual banned-substance review on analytical approaches in human sports drug testing is dedicated to literature published between October 2023 and September 2024. As in previous years, focus is put particularly on new or enhanced analytical options in human doping controls as well as investigations into the metabolism and elimination of compounds of interest, which represent central (while not exclusive) cornerstones of the global anti-doping mission. New information published within the past 12 months on established doping agents as well as new potentially relevant substances are reviewed and discussed in the context of the World Anti-Doping Agency's 2024 Prohibited List. Thereby, analytical challenges, especially with regard to the continuously growing number of target compounds and potentially relevant drug classes as well as the exigency (and consequences) of utmost analytical retrospectivity, are thematized and contextualized. Investigations especially into anabolic agents, peptide hormones, and strategies for the detection of gene doping were identified as core areas of anti-doping research in the reviewed period.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manuela Carla Monti, Melanie Bauer, Konrad Koch, Eva Scheurer, Götz Schlotterbeck
{"title":"Evaluation of ATR-FTIR, HPLC-DAD, GC-MS, and GC-IR for the Analysis of 145 Street Drug Samples From Drug Checking Services.","authors":"Manuela Carla Monti, Melanie Bauer, Konrad Koch, Eva Scheurer, Götz Schlotterbeck","doi":"10.1002/dta.3843","DOIUrl":"https://doi.org/10.1002/dta.3843","url":null,"abstract":"<p><p>Drug checking services (DCS) are entities that allow recreational drug users to have street drug samples analyzed. Diverse analytical methods are applied for DCS, ranging from test strips to mass spectrometry (MS). This work evaluates the performance and utility of common methodologies used for DCS operating with off-site drug testing, while additionally assessing the potential of gas chromatography coupled to vapor phase infrared spectroscopy (GC-IR). Gas chromatography MS (GC-MS), GC-IR, and high-performance liquid chromatography with diode array detector (HPLC-DAD) were evaluated based on the analysis of 145 street drug samples obtained from two Swiss DCS. Additionally, attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) was applied and is briefly discussed. A combined total of 245 analytes (including adulterants and cutting agents) were detected. GC-MS presented the greatest number of detected compounds, with a sensitivity of 96% compared with the sum of all analytes, followed by HPLC-DAD with 82%, while GC-IR showed limited sensitivity with 70%. GC-IR underperformed regarding the detection of low-abundant adulterants and of the main active ingredients in strongly adulterated samples. This study discusses the limitations and strengths of the evaluated methods in the specific context of DCS, while providing insights into the occurrence of false declarations (differing analytical results compared with alleged drug identity) and the distributions of adulterants and cutting agents in street drug samples. Based on our results, complementary approaches are considered the most valuable. Finally, the promotion of comprehensive guidelines regarding the quality and suitability of analytical methods for DCS would be highly desired.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detection of Oral Testosterone Undecanoate Administration in UGT2B117 del/del and del/ins Individuals. Part I: Urinary Steroid Profile and IRMS Markers.","authors":"Sergi Coll, Sho Shiomura, Élida Alechaga, Claudia Bressan, Núria Monfort, Rosa Ventura, Masato Okano","doi":"10.1002/dta.3846","DOIUrl":"https://doi.org/10.1002/dta.3846","url":null,"abstract":"<p><p>The detection of endogenous anabolic androgenic steroids misuse in Asian population using the Steroidal Module of the Athlete Biological Passport (ABP) is a challenge due to the high prevalence of UGT2B17 gene deletion polymorphism and low levels of testosterone (T) glucuronide. In this study, the capabilities of different approaches based on urine analysis for detecting oral T undecanoate administration were evaluated in 13 Asian volunteers, including 11 subjects with del/del genotype and 2 subjects with del/ins genotype. In this part of the work, the effect on the urinary steroid profile (SP) and the isotope ratio mass spectrometry (IRMS) markers were studied. Results showed that the 5α-androstane-3α,17β-diol/epitestosterone ratio is the most sensitive marker of the SP to detect oral T administration in Asian volunteers. All urines that led to suspicious urinary SP were concluded IRMS positive. However, for some subjects, the ABP Steroidal Module was unable to identify suspicious samples that were still detectable by IRMS. Positive IRMS samples were detected up to 24 h (n = 9), 36 h (n = 3), or 48 h (n = 1) after oral administration. Overall, the urinary SP together with IRMS allowed the detection of T administration in Asian volunteers. However, the detection windows are short, as reported for oral T administration in Caucasian volunteers. These findings highlight the need of implementing additional markers in the Steroidal Module of ABP that could enlarge detection windows.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detection of Oral Testsosterone Undecanoate Administration in UGT2B17 del/del and del/ins Individuals. Part II: Urinary Endogenous Steroid Sulfate Markers.","authors":"Sergi Coll, Sho Shiomura, Élida Alechaga, Claudia Bressan, Núria Monfort, Masato Okano, Rosa Ventura","doi":"10.1002/dta.3845","DOIUrl":"https://doi.org/10.1002/dta.3845","url":null,"abstract":"<p><p>The detection of endogenous anabolic androgenic steroids misuse in Asian population using the Steroidal Module of the Athlete Biological Passport (ABP) is a challenge due to the high prevalence of UGT2B17 gene deletion polymorphism with low levels of testosterone (T) glucuronide. In this study, the capabilities of different approaches based on urine analysis for the detection of oral T undecanoate administration were evaluated in 13 Asian volunteers, including 11 subjects with del/del genotype and 2 subjects with del/ins genotype. In the first part of the work, the effect on the urinary steroid profile (SP) and on the isotope ratio mass spectrometry markers was evaluated. In this second part, the effect on endogenous sulfate markers was evaluated. Results showed that the oral T administration is detected for a much longer period of time with sulfate markers than with the conventional urinary SP markers. Androstanediol sulfate 1 (Diol-S1)/dehydroandrosterone sulfate (DHA-S) and epiandrosterone sulfate (epiA-S)/DHA-S ratios were the most diagnostic parameters for longitudinal monitoring, as reported for Caucasian volunteers in a previous work. For most subjects, sulfate markers allowed the detection of suspicious samples up to 144 h. Combinations of sulfate and glucuronide markers improved the sensitivity in comparison with the conventional SP markers, but yielded poorer results than the best sulfate ratios. Based on the results of this study and previous works, sulfate EAAS metabolites provide a consistent improvement in the detectability of T administration in both Caucasian and Asian populations. Their incorporation into the ABP should be considered.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jenny K Y Wong, Timmy L S Choi, Celia O L Wong, Peter Curl, Terence S M Wan, Emmie N M Ho
{"title":"Doping Control Analysis of Methylsulfonylmethane in Horses.","authors":"Jenny K Y Wong, Timmy L S Choi, Celia O L Wong, Peter Curl, Terence S M Wan, Emmie N M Ho","doi":"10.1002/dta.3844","DOIUrl":"https://doi.org/10.1002/dta.3844","url":null,"abstract":"<p><p>Methylsulfonylmethane (MSM), also known as dimethyl sulfone, is a naturally occurring sulphur-containing compound that can be found in plants, animals and humans. MSM can also be a metabolite of dimethyl sulfoxide (DMSO). Due to their anti-inflammatory and analgesic effects, both MSM and DMSO are prohibited substances in horseracing. As both substances are naturally occurring, their misuse in horses is controlled by International Residue Limits (IRL) of 1200 and 15 μg/mL, respectively, in horse urine as established by the International Federation of Horseracing Authorities. The elimination of DMSO in horses has been reported; however, there has been no report on the elimination of MSM in horses. This paper describes a pilot study of an administration study of MSM in two geldings following one scoop (~15 g) of Pure MSM twice daily for six consecutive days. MSM in post-administration urine and blood samples was quantified by gas chromatography-mass spectrometry after sample dilution, with additional protein precipitation for the blood samples. The elimination profiles of MSM in urine and blood are described. The maximum detection time in urine at the IRL of 1200 μg/mL was around 4.5 days after the last dose. Plasma MSM in both horses was around 120 μg/mL at 4.4 days after the last dose, which was the last blood sample collected. As such, 120 μg/mL may indicate a possible IRL for controlling MSM in horse blood. The analysis of DMSO in post-MSM-administration samples showed that DMSO is not a significant metabolite of MSM in horses.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Celine Vanhee, Maarten Dill, Michael Canfyn, Emmy Tuenter, Sophia Barhdadi
{"title":"The Emergence of a Novel Synthetic Nicotine Analog 6-Methyl Nicotine (6-MN) in Proclaimed Tobacco- and Nicotine-Free Pouches Available in Europe.","authors":"Celine Vanhee, Maarten Dill, Michael Canfyn, Emmy Tuenter, Sophia Barhdadi","doi":"10.1002/dta.3841","DOIUrl":"https://doi.org/10.1002/dta.3841","url":null,"abstract":"<p><p>A new nicotine delivery system in the form of tobacco-free nicotine pouches was introduced in Europe in 2019. These nicotine bags did not fall under the Tobacco Products Directive (TPD) II, which brought forward regulatory requirements for both cigarettes, related products, and e-liquids. As these pouches did not fall under the scope of the TPD, it was up to the member states to decide which action to be taken if any. Some EU member states banned these nicotine pouches, while others put restrictions on the amount of nicotine, warning messages, and presentation and packaging of the product, and some member states did not take any action. Likely as a result of the ban or restrictions, soon after also, tobacco and nicotine-free pouches became available in the European Union (EU). Early 2024, \"NoNIC\" pouches, claiming to be tobacco- and nicotine-free, became available on the European market. These pouches are promoted online and clearly target a younger population with a youth-appealing package design and enticing flavors. Upon analysis of different samples utilizing gas chromatography coupled to MS (GC-MS), liquid chromatography coupled to high-resolution tandem mass spectrometry (HRAM LC-MS2), and nuclear magnetic resonance spectroscopy (NMR), it was demonstrated that these pouches were indeed devoid of nicotine but contained the synthetic nicotine homolog 6-methyl nicotine (6-MN) and this up to 20 mg per pouch. Nonetheless, a part of a likely unaware/misled young adult subpopulation has easy access to these products, containing a novel molecule for which limited to no clinical effects are known.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lydia Brooks, Michael Ryan, Erin McCosham, Devan Loganathan
{"title":"Further Investigation Into an Environmental Source for Aminorex.","authors":"Lydia Brooks, Michael Ryan, Erin McCosham, Devan Loganathan","doi":"10.1002/dta.3820","DOIUrl":"https://doi.org/10.1002/dta.3820","url":null,"abstract":"<p><p>In 2009, levamisole was identified as a source for several aminorex positives reported in postrace equine samples in Canada. Since then, unexplained detections of aminorex continue to be identified in equine samples where there is no evidence to link these detections to a levamisole administration. Previous studies identified a compound named barbarin in some species of plants from the Brassicaceae family and suggested that barbarin may be a possible precursor for aminorex. The objectives of this study were to (1) investigate the link between barbarin and aminorex and (2) identify other biomarkers of plant origin. Methods were developed and validated for the detection of aminorex, barbarin, glucobarbarin, and other associated compounds. Aminorex was administered to one horse, and barbarin was not detected in any plasma and urine samples. Barbarea stricta and Barbarea orthoceras were administered to two horses, and aminorex was detected in all plasma and urine samples collected. Barbarin was detected in some plasma but not in urine samples. Resedine was observed in retrospective examination of chromatograms of the plant material and from all plants postadministration plasma and urine samples from the two horses. Resedine was administered to one horse and was detected in plasma and urine samples, but aminorex was only detected in urine samples. These results provide evidence that resedine is an intermediary compound between barbarin and aminorex in horses and that resedine can be used as a biomarker to eliminate the reporting of aminorex positives originating from the ingestion of plants from the Brassicaceae family.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}