Enhanced UHPLC-MS/MS screening of selective androgen receptor modulators following urine hydrolysis

Gadaj, Anna; Ventura, Emiliano; Healy, Jim; Botrè, Francesco; Sterk, S.S.; Buckley, Tom; Mooney, Mark

doi:10.1016/j.mex.2020.100926

Cited by 11 publications

(8 citation statements)

References 10 publications

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“…Thevis et al 24 summarized fragmentation patterns after electrospray ionization (ESI), collision‐induced dissociation (CID), and electron ionization (EI) of representatives from each category of SARMs. Using ultra performance liquid chromatography ‐ tandem mass spectrometer, Gadaj et al 25 had improved sensitivity for detecting SARMs after enzymatic hydrolysis of urine sample components.…”

Section: Introductionmentioning

confidence: 99%

Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control

Karatt

Sathiq

Laya

et al. 2023

Rapid Comm Mass Spectrometry

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Since 2010, there has been an increasing number of adverse analytical findings related to selective androgen receptor modulators (SARMs) in competitive sports. It emphasizes the importance of comprehensive doping control analytical procedures that are capable of detecting SARM misuse.Methods: In this study, it is described how LY2452473, a SARM, was metabolized in thoroughbred horses after a single-dose oral administration and in vitro with equine liver microsome preparations. An investigation of the metabolism of LY2452473 in horses' urine, plasma, and hair matrices was carried out during the study. The plausible structures of the detected metabolites were postulated using highperformance liquid chromatography-high resolution mass spectrometry.Results: Under the experimental conditions 15 metabolites (12 phase I and three conjugates of phase I) were detected (M1-M15). The major phase I metabolites identified were formed by hydroxylation. Side-chain dissociated and methylated metabolites were also detected. In phase II, the glucuronic acid and sulfonic acid conjugates of hydroxy LY2452473 were detected as the major metabolites. In vitro analysis has confirmed the presence of all metabolites found in vivo except for the methylated analogs M11 and M12. A peak concentration of LY2452473 (0.5 pg/mg) in proximal hair segments was achieved 4 weeks after administration, according to hair analysis.Conclusions: Data obtained will aid in identifying LY2452473 and related substances faster. Furthermore, the results will assist in checking for the illegal use of these substances in competitive sports. | INTRODUCTIONThe role of androgens in male sexual development and maintenance cannot be overstated. 1 Androgens are predominant in male reproductive organs, but also moderately expressed in female genitalia and ovaries, as well as in skin, sebaceous glands, sweat glands, hair follicles, cardiac muscles, skeletal muscles, and brain. 2 A risk of serious side effects, such as prostate cancer development and progression, has limited the use of steroidal androgens. [3][4][5] Selective androgen receptor modulators (SARMs) are tissue-specific to anabolic target tissues (muscle and bone) and do not have the side effects associated with conventional androgens. The basic idea of the SARMs is that they modulate the transcriptional activity of the androgen receptor in a tissue-selective fashion. These compounds are agonistic in their effects on target tissues such as muscle and bone, but weak in their effects on reproductive organs (prostate). The molecular

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Section: Introductionmentioning

confidence: 99%

Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control

Karatt

Sathiq

Laya

et al. 2023

Rapid Comm Mass Spectrometry

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“…Analytical approaches for detecting steroids and SARMs mostly involve multi-analysis liquid chromatography and analysis using mass spectrometry 15,16 from various matrices containing steroids and SARMs such as dietary supplements, urine, serum and hair. [17][18][19][20][21][22] However, the analytical information about each compound for accurate screening and identification showing structural compounds without reference standards is still insufficient.…”

Section: Introductionmentioning

confidence: 99%

Application of predicted fragmentation pathways and fragment ion structures for detecting steroids and selective androgen receptor modulators in dietary supplements using liquid chromatography–quadrupole time‐of‐flight mass spectrometry

Kim

Lim

Choi

et al. 2022

Rapid Comm Mass Spectrometry

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Rationale Dietary supplements advertised to strengthen muscles have earned fame among athletes. However, several products containing unauthorized compounds are often detected, which can cause a public health risk. Particularly, steroids and selective androgen receptor modulators (SARMs) can cause serious side effects as hormone modulators. In this study, we analyzed 15 steroids and 20 SARMs using liquid chromatography–quadrupole time‐of‐flight mass spectrometry (LC/QTOFMS) to provide fundamental information about fragmentation pathways and fragment ion structures. Methods The optimal conditions of LC/QTOFMS were explored to obtain fragmentation patterns for each compound. The optimal conditions were established by comparing the area and height of the precursor ion peak at 125 or 175 V as a fragmentor energy. Furthermore, the optimized spectra were acquired by applying collision energy ranging from 1 to 50 eV. The energy value was selected under the condition that the mass error of precursor ions was less than 10 ppm. Results The 35 compounds were classified on the basis of their chemical core structures: arylpropionamide (3 compounds), quinolinone (2), pyrrolidinylbenzonitrile (1), indole (2), tropanol (2), phenylaxadaizole (1), hydantoin (2), phenylthiazole (1), nitrothiophene (1) and steroidal derivative (20). Fragmentation pathways and the chemical structure of each product ion were predicted and identified. Furthermore, the obtained structural information was applied to screen seized samples. As a result, 10 seized samples were confirmed to contain one or more SARMs by comparing each precursor ion and fragmentation pattern. Conclusions The application to real samples for accurate screening indicated that the same fragmentation patterns and product ions as one or more SARM standards were detected and identified in the seized samples advertised as muscle building. Therefore, this study can contribute to ensuring the safety of public health through providing fundamental information about the risk of illegal adulteration.

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“…Thevis and Volmer studied fragmentation patterns of three selected SARMs drug candidates, GSK2881078, PF-06260414 and TFM-4 using both Liquid Chromatography Mass Spectrometry (LC-MS/MS) and Gas Chromatography Mass Spectrometry (GC-MS/MS), showing the mass spectral data for these substances in order to support the development of new methods and research of drug metabolism [28]. Gadaj et al detected 14 SARMs in urine from different species, including humans, using semi-quantitative LC-MS/MS with Limit of Detection (LOD) range from 0.002 to 0.2 ng/ml [29]. Rading et al investigated the in vivo metabolism of GSK2881078 after single oral administration and analyzing urine and hair matrices [30].…”

Section: Analytical Dimensions Of International Standard For Prohibit...mentioning

confidence: 99%

Olympic Anti-Doping Laboratory: The Analytical Technological Road From 2016 Rio De Janeiro to 2021 Tokyo

et al. 2021

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The summer Olympic Games is the major mega sports event since the first modern era Olympiad, held in Athens, Greece in 1896. International Olympic Committee (IOC) has the responsibility of the organization of the summer and winter Games ensuring the broadcast in all corners of earth. The World Anti-Doping Agency (WADA) is the responsible organization of the fight against doping in sports. IOC and WADA support the event's country WADA Accredited Laboratory to incorporate the maximum of the new analytical technologies to become applicable during the event's antidoping testing. The current study reviewed the last 5 years progresses of the antidoping system with emphasis on the laboratory field.

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Enhanced UHPLC-MS/MS screening of selective androgen receptor modulators following urine hydrolysis

Cited by 11 publications

References 10 publications

Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control

Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control

Application of predicted fragmentation pathways and fragment ion structures for detecting steroids and selective androgen receptor modulators in dietary supplements using liquid chromatography–quadrupole time‐of‐flight mass spectrometry

Olympic Anti-Doping Laboratory: The Analytical Technological Road From 2016 Rio De Janeiro to 2021 Tokyo

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