Masato Okano, Yuma Watanabe, Asami Miyamoto, Masanori Ota, Mitsuhiko Sato
{"title":"Distinguishing Between Oral and Transdermal Administration Routes of Methyltestosterone Through Human Urine and Dried Blood Spot Analyses for Doping Control Purposes.","authors":"Masato Okano, Yuma Watanabe, Asami Miyamoto, Masanori Ota, Mitsuhiko Sato","doi":"10.1002/dta.3962","DOIUrl":"https://doi.org/10.1002/dta.3962","url":null,"abstract":"<p><p>Unintentional doping violations have been reported after secondary skin exposure, including partner contact or contact sports. Methyltestosterone (MT), an anabolic androgenic steroid on the World Anti-Doping Agency Prohibited List, is readily available in Japan as an over-the-counter topical hair-growth preparation and as oral tablets. This study evaluated whether transdermal absorption of MT can be distinguished from oral administration using human urine and dried blood spot (DBS) analyses. Ten men received MT once daily for five consecutive days (five oral, five transdermal). The urinary tetrahydro-metabolites 17α-methyl-5α-androstane-3α,17β-diol (5α-THMT) and 17α-methyl-5β-androstane-3α,17β-diol (5β-THMT) were detectable within hours after administration for both routes. Following transdermal administration, 5α-THMT remained detectable up to 97 h after the final administration, whereas, after oral administration, 5β-THMT persisted longer, up to 265 h. Transdermal application produced a marked increase in 5α-THMT, consistent with high 5α-reductase activity in skin, yielding a significantly higher 5α-THMT/5β-THMT ratio than after oral administration. Nonetheless, individuals with inherently high 5α-reductase activity may exhibit elevated ratios even after oral dosing, warranting careful interpretation. In DBS after oral dosing, parent MT was generally detectable up to 24 h, providing a shorter detection window than urinary tetrahydro-metabolites. Overall, combining urine (tetrahydro-metabolites) and DBS (parent MT) analyses enables effective detection of MT use and supports differentiation of administration routes.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342168","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}
Olivier Salamin, Joséphine Chappuis, Lasse V Bækken, Tiia Kuuranne, Nicolas Leuenberger
{"title":"CERA Detection and Stability in Blood Versus Urine.","authors":"Olivier Salamin, Joséphine Chappuis, Lasse V Bækken, Tiia Kuuranne, Nicolas Leuenberger","doi":"10.1002/dta.3960","DOIUrl":"https://doi.org/10.1002/dta.3960","url":null,"abstract":"<p><p>Erythropoietin receptor agonists (ERAs), including continuous erythropoietin receptor activators (CERAs), are potent blood doping substances used to enhance endurance performance by stimulating erythropoiesis. While traditionally detected through direct analysis of urine or serum samples using sarcosyl-polyacrylamide gel electrophoresis (SAR-PAGE) and western blotting, the slow urinary elimination of third-generation ERAs like CERA has shifted anti-doping strategies toward serum-based detection. This study compared the detectability and stability of CERA in urine and serum matrices and evaluated the added value of combining direct detection with hematological profiling. Using samples from a controlled CERA administration study and an authentic case example, we assessed CERA detection in serum, urine, and simulated dried blood spot (DBS) matrices (Tasso-M20). Additionally, we conducted stability experiments by incubating spiked matrices at 37°C for up to 72 h. Our results confirmed the superior stability and consistent detectability of CERA in serum and DBS compared with urine. Moreover, hematological alterations such as increased reticulocytes percentage flagged by the Athlete Biological Passport (ABP) supported targeted serum testing, leading to the successful detection of CERA. These findings highlight the importance of systematic blood collection for both direct and indirect detection strategies. Furthermore, DBS samples showed promising analytical performance and resistance to elevated temperature, suggesting their utility as minimally invasive alternatives in anti-doping programs. Overall, our study reinforces the relevance of blood matrices in the detection of CERA and advocates for the broader integration of blood-based strategies in targeting doping practices with ERAs.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342222","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}
Jenna M Goodrum, Vinod S Nair, Andre K Crouch, Daniel Eichner, Geoffrey D Miller
{"title":"Evaluating the Testosterone-to-Luteinizing Hormone Ratio in Male Anti-Doping Serum Samples: Results From a Transdermal Testosterone Administration Trial and Field Collected Samples.","authors":"Jenna M Goodrum, Vinod S Nair, Andre K Crouch, Daniel Eichner, Geoffrey D Miller","doi":"10.1002/dta.3959","DOIUrl":"https://doi.org/10.1002/dta.3959","url":null,"abstract":"<p><p>The serum testosterone-to-luteinizing hormone (T/LH) ratio has previously been suggested as a sensitive marker of testosterone use in an anti-doping setting. When measured with an automated immunoassay platform, this ratio represents a quick and cost-effective screening biomarker to further direct isotope ratio mass spectrometry (IRMS) testing efforts in concurrently collected urine samples to confirm testosterone abuse. To evaluate the practicality of implementing the serum T/LH ratio for routine use, testosterone values in 356 serum samples were compared between a \"gold-standard\" LC-MS/MS method and an automated immunoassay method. Excellent correlation and minimal bias between the two methods were observed, highlighting the validity of the immunoassay method. Next, a testosterone administration study utilizing a transdermal delivery route was conducted to compare the effectiveness of the serum T/LH ratio to the currently used serum testosterone to androstenedione (T/A4) and urinary testosterone to epitestosterone (T/E) ratios. The serum T/LH ratio was more sensitive than the T/A4 ratio and showed similar sensitivity to the urinary T/E ratio with high interindividual variability. Finally, T/LH analysis was conducted on 626 capillary serum samples collected in the field from male Ultimate Fighting Championship athletes. Of the three samples that showed elevated T/LH ratios in this pool, two of the corresponding urine samples were IRMS positive, one of which showed an unremarkable urinary T/E ratio and relatively normal steroid profile. These results indicate serum T/LH ratio monitoring provides a beneficial addition to the anti-doping tool kit and can improve urinary IRMS testing recommendations.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290440","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}
Abdul Khader Karakka Kal, Michael Benedict Subhahar, Moses Philip, Fatma Mohammed Graiban, Tajudheen K Karatt, Binoy Mathew, Ringu Mareena George, Balakrishnan Maruthasalam
{"title":"Equine Metabolism of Voxelotor and Its Impact on Hematological Indices: A Doping Control Perspective.","authors":"Abdul Khader Karakka Kal, Michael Benedict Subhahar, Moses Philip, Fatma Mohammed Graiban, Tajudheen K Karatt, Binoy Mathew, Ringu Mareena George, Balakrishnan Maruthasalam","doi":"10.1002/dta.3957","DOIUrl":"https://doi.org/10.1002/dta.3957","url":null,"abstract":"<p><p>Voxelotor, a therapeutic drug for sickle cell disease, has been reported to elevate serum erythropoietin and hemoglobin levels in healthy individuals. Because of its potential to alter blood parameters, the World Anti-Doping Agency (WADA) classified voxelotor under category M1 of the 2023 Prohibited List. Despite this classification, little is known about its metabolic behavior in either humans or animals. In this study, the metabolism of voxelotor was investigated in Thoroughbred horses after oral administration. Using liquid chromatography high-resolution mass spectrometry (LC-HRMS), 35 metabolites were detected. Among them, the most prominent pathways included hydroxylation and reductive transformations (Phase I), as well as glucuronidation and sulfonation (Phase II). Notably, several glucuronide conjugates and hydroxylated derivatives were identified as major metabolites, with extended detection times that make them particularly relevant for antidoping surveillance. Blood analyses also revealed changes in red blood cell count, hemoglobin concentration, packed cell volume, and platelet levels. Together, these findings provide practical insight into voxelotor's metabolic profile in equines and highlight specific metabolites useful for doping control. Further studies are needed to better define its hematological impact and to confirm whether the observed clinical effects are drug related.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249026","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}
Kathrine B Faldborg, Jørgen B Hasselstrøm, Thomas Kraemer, Charlotte U Andersen, Andrea E Steuer
{"title":"Prolonged Detection of GHB Intake in Urine: Are We Finally There?","authors":"Kathrine B Faldborg, Jørgen B Hasselstrøm, Thomas Kraemer, Charlotte U Andersen, Andrea E Steuer","doi":"10.1002/dta.3956","DOIUrl":"https://doi.org/10.1002/dta.3956","url":null,"abstract":"<p><p>Gamma-hydroxybutyric acid (GHB) has been implicated in drug-facilitated sexual assault (DFSA). However, due to its rapid elimination and the challenge of distinguishing exogenous from endogenous levels, GHB is likely to be significantly underestimated in DFSA cases. Consequently, previous research has focused on identifying biomarkers associated with GHB intake that persist longer than GHB itself. Conjugates of GHB with amino acids and pentose have been proposed as potential candidates, but data on their detection times remain limited. In this study, a randomised, placebo-controlled trial involving 30 healthy volunteers was conducted. Urine samples were collected at regular intervals over 5 days post-administration. Using a validated LC-MS/MS method, we quantified known and proposed GHB biomarkers, aiming to identify those capable of extending the detection window. GHB-amino acid conjugates showed limited utility beyond early time points, whereas a tentatively identified GHB-pentose emerged as a very promising marker. With structural confirmation and further validation, it may allow reliable detection for at least 24 h after intake, representing a significant advance in DFSA investigations.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231171","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}
Kim Petterson Bohlin, Tomas Villén, Oscar Hopcraft, Anton Pohanka, Lena Ekström
{"title":"Prevalence of AAS-Positive Samples at Drug Abuse Laboratory Sweden Between 2014 and 2023 and Sub-Study of Dual Use of AAS and Narcotics.","authors":"Kim Petterson Bohlin, Tomas Villén, Oscar Hopcraft, Anton Pohanka, Lena Ekström","doi":"10.1002/dta.3955","DOIUrl":"https://doi.org/10.1002/dta.3955","url":null,"abstract":"<p><p>It is of interest to investigate trends in AAS usage profile. Here we aimed to retrospectively study the prevalence of AAS-positive samples based on 21,172 consecutive analyses from routine AAS testing 2014-2023. Moreover, 310 urine samples from 2022 to 2023 were reanalyzed for a broader AAS panel as well as for the presence of narcotics. Between 2014 and 2023, the frequency of reported AAS-positive samples varied between 6% and 11%, with no trend discerned. The prevalence of samples containing several AAS also shows a similar distribution. The most common AAS detected were consistently testosterone, nandrolone, and drostanolone. Of the 310 urine samples reanalyzed, 80 male and 6 female samples were positive for AAS. Thirteen of the samples showed T/E 4-10, indicative of testosterone use, with no other AAS. Consequently, 4% of the samples might have been reported as false negatives. Of the AAS-positive samples, amphetamine was found in 10% and 0% of the male and female samples, respectively. Cannabis was more often detected in AAS-positive female samples (50%) than in male samples (25%), whereas cocaine was more commonly detected in male than in female samples (33 versus 17%). The prevalence of cannabis and amphetamine was like previous AAS studies conducted in Sweden, whereas the presence of cocaine in male samples was substantially higher. Co-use of AAS and narcotics is a well-known problem and highlights the importance of preventive actions and education/awareness of AAS.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135906","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}
C Cloteau, V Delcourt, B Loup, B Chabot, M Pescher, E Susdorf, Z Kaabia, P Garcia, M A Popot, B Le Bizec, G Dervilly, L Bailly-Chouriberry
{"title":"Identification of Candidate Biomarkers Detected in the Urine of Racehorses After Anabolic Agent Administration: Use of Orthogonal Methods for Structural Elucidation.","authors":"C Cloteau, V Delcourt, B Loup, B Chabot, M Pescher, E Susdorf, Z Kaabia, P Garcia, M A Popot, B Le Bizec, G Dervilly, L Bailly-Chouriberry","doi":"10.1002/dta.3951","DOIUrl":"https://doi.org/10.1002/dta.3951","url":null,"abstract":"<p><p>Biomarker identification by mass spectrometry represents a key step in the workflow of nontargeted metabolomic studies. Given the complexity of the data, this step, which must be carried out by a trained specialist, is time-consuming, and the biomarkers discovered are not always identified. While this stage is not an obstacle to the development of new screening and classification tools, it is nonetheless crucial to a better understanding of the results obtained. For this reason, the aim of this study was to perform structural elucidation of candidate biomarkers, which had previously been displayed to screen for the administration of anabolic agents in the urine of racehorses and whose robustness had been evaluated. The present study involved a combination of various analytical strategies, including enzymatic hydrolysis, high-resolution mass spectrometry and ion mobility (LC-HRMS, LC-IMS-HRMS), and in vitro experiments. Two candidate biomarkers were identified as phase II metabolites of tebuconazole, belonging to the equine exposome. This identification opens the way to further investigations into the relationship between the presence of this compound and its disruption in horse urine following anabolic agent administration. Overall, the use of orthogonal approaches provided better complementary information on the structure of the compound and ultimately enabled us to identify biomarkers with the highest possible level of confidence.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084579","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}
Xavier de la Torre, Cristiana Colamonici, Dayamin Martínez Brito, Rodny Montes de Oca Porto, Francesco Botrè
{"title":"Clostebol Metabolism by Different Routes of Administration: Selection of Diagnostic Urinary Markers.","authors":"Xavier de la Torre, Cristiana Colamonici, Dayamin Martínez Brito, Rodny Montes de Oca Porto, Francesco Botrè","doi":"10.1002/dta.3953","DOIUrl":"https://doi.org/10.1002/dta.3953","url":null,"abstract":"<p><p>The accidental contamination by the use of transdermal applications of clostebol acetate has been proven by the monitoring of its main urinary metabolite 4-chloro-3α-hydroxy-androst-4-en-17-one (M1). This work is aimed at describing clostebol metabolism in humans and at searching for specific metabolic markers or concentration thresholds allowing for distinguishing between an oral and a transdermal administration, helping to set up adequate criteria to be adopted by the antidoping community when incidental contamination is suspected. Urine samples were collected after the administration of a single dose of clostebol acetate orally (n = 3, males), a single transdermal dose (n = 1, male), and multiple transdermal administrations (n = 3, males, and n = 3, females). After enzymatic hydrolysis, liquid-liquid extraction, and the formation of trimethylsilyl derivatives, the samples were analyzed by gas chromatography coupled to tandem mass spectrometry and time-of-flight mass spectrometry. The metabolism of clostebol after oral and transdermal applications was described. Ten metabolites were detected after oral administration (M1-M10), but only five (M1-M4 and M9) could be detected after transdermal applications under the assay conditions applied. The use of concentrations of any metabolite might be difficult because of the interindividual variability in absorption, metabolism, and/or excretion. Instead, the ratios between M4 and M1 showed plausible results to discriminate between both administrations under the conditions described here. The intentionality of the use of one or other route of administration cannot be assessed.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068771","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":"Comparative Evaluation of Smart Sampling for hCG Determination: A New Potential Direction in Protein Biomarker Analysis From Dried Microsamples.","authors":"Ago Mrsa, Marijana Matijevic, Yvette Dehnes, Trine Grønhaug Halvorsen, Léon Reubsaet","doi":"10.1002/dta.3948","DOIUrl":"https://doi.org/10.1002/dta.3948","url":null,"abstract":"<p><p>Since the early 20th century, sampling biological matrices like blood on paper (dried blood spots [DBS]) has been vital in clinical analysis. While DBS microsampling is convenient for small molecules, extensive sample preparation can make LC-MS protein analysis impractical because of the time-consuming steps, especially for low-abundance proteins. Smart sampling, introduced in 2018, simplifies this by integrating sample preparation directly on the sampler. The work presented in this paper aims to compare a newly validated smart sampling method with two other methods: an in-house method based on immunocapture on magnetic beads and a commercial method that uses electrochemiluminescence immunoassay (ECLIA). The performance of the three hCG methods was compared using 21 single-blind serum samples. Linear regression analysis revealed strong correlations (all R<sup>2</sup> > 0.91) between the actual sample concentrations and the results obtained from all three methods. Immunocapture with magnetic beads showed the strongest linear correlation (R<sup>2</sup> = 0.974). To assess agreement between the methods, Bland-Altman analysis was conducted. The comparison between smart sampling and magnetic beads showed an average bias of -5.2, with no significant trend in variation across the sample concentration range of 0.5-75 ng/mL. The smart sampling and ECLIA comparison revealed a bias of 0.4 ± 4 ng/mL, indicating even better agreement and consistent results. This paper presents the first-ever comparison of a smart sampling method with existing methods. The results highlight smart sampling as a promising new approach for bioanalysis and boost the technique as a viable alternative in protein biomarker analysis from complex matrices using LC-MS.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063058","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}
Abhishek Gour, Sushobhan Mukhopadhyay, Allison Henderson, Ahmed Awad, Maria A Seabra, Mallory Pullman, Francisco León, Stephen J Cutler, Christopher R McCurdy, Abhisheak Sharma
{"title":"From Kratom to Semi-Synthetic Opioids: The Rise and Risks of MGM-15.","authors":"Abhishek Gour, Sushobhan Mukhopadhyay, Allison Henderson, Ahmed Awad, Maria A Seabra, Mallory Pullman, Francisco León, Stephen J Cutler, Christopher R McCurdy, Abhisheak Sharma","doi":"10.1002/dta.3952","DOIUrl":"https://doi.org/10.1002/dta.3952","url":null,"abstract":"<p><p>Kratom (Mitragyna speciosa), a plant native to Southeast Asia, has long been used for its stimulant and analgesic properties. 7-Hydroxymitragynine (7-HMG) is a potent and selective opioid agonist in vitro and demonstrates a potent opioid effect in living subjects, reversible by naloxone. It has been semi-synthesized into products that are readily available in retail and virtual shops. It is known that 7-HMG has earned the nickname \"legal morphine,\" and has gained popularity among users seeking pain relief and/or a \"high\" comparable with prescription opioids. Medicinal chemistry efforts have led to synthetic 7-HMG derivatives such as MGM-15, where stereospecific saturation of the imine N(1)-C(2) double bond increases opioid receptor affinity and activity. Despite its higher in vitro opioid potency, MGM-15 is currently sold in the US for human consumption as a \"research chemical\" in tablet form, even though there is an absence of this being studied in humans and obviously no FDA approval. In this study, we analyzed commercially available MGM-labeled tablets using UPLC-MS/MS and subsequently evaluated the binding affinities of purified MGM-15 across multiple opioid receptors. Tablets contained an average of 10.9 ± 0.2 mg (10.7 to 11.2 mg) of MGM-15, with no naturally occurring kratom alkaloids or illicit substances detected. MGM-15 shows greater hMOR and hDOR binding affinities than 7-HMG, indicating the potential for higher opioid effects and risks, emphasizing the urgent need for more research to advise regulation and hopefully prevent misuse and harm.</p>","PeriodicalId":160,"journal":{"name":"Drug Testing and Analysis","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038709","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}