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Application of Simultaneous Analytical Methods for Selective Androgen Receptor Modulator Adulterated in Dietary Supplements Advertised as Muscle Strengthening Using UHPLC-PDA and LC–ESI–MS/MS

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Abstract

Recently, the selective androgen receptor modulators (SARMs) have been popular among athletes due to their muscle strengthening effects. However, it has been often reported that the unauthorized compounds like SARMs were illegally adulterated in dietary supplements and were misused to improve their pharmacological efficacies. To analyse and reconfirm the SARMs adulterated in dietary supplements, we developed and optimised a rapid and accurate method to measure 18 SARMs simultaneously using an ultra-high-performance liquid chromatography system equipped with a photodiode array detector and liquid chromatography-electrospray ionization-tandem mass spectrometry. The simultaneous methods were validated to fully meet the international guidelines by determining the limit of detection, limit of quantification, method detection limit, method quantitation limit, specificity, linearity, precision, accuracy, recovery, stability, and matrix effect. In addition, the validated methods were used for application to 75 real samples containing dietary supplements and seized samples. On screening 18 compounds, a total 10 SARMs (MK-677, YK-11, etc.) were detected in 25 seized hard capsule samples by comparing the UHPLC-PDA and LC–ESI–MS/MS. In addition, the concentrations of adulterants in seized hard capsule samples ranged from minimum at 2.14 µg g−1 of LGD-4033 and maximum at 71,989 µg g−1 of andarine. The established simultaneous analysis method could help to investigate the unauthorized compounds adulterated in various types of dietary supplement.

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Data availability statement

The data that support the findings of this study are available in the supplementary material of this article.

References

  1. Leaney AE, Beck P, Biddle S, Brown P, Grace PB, Hudson SC, Mawson DH (2020) Analysis of supplements available to UK consumers purporting to contain selective androgen receptor modulators. Drug Test Anal. https://doi.org/10.1002/dta.2908

    Article  PubMed  Google Scholar 

  2. Geyer H, Schanzer W, Thevis M (2014) Anabolic agents: recent strategies for their detection and protection from inadvertent doping. Br J Sports Med. https://doi.org/10.1136/bjsports-2014-093526

    Article  PubMed  Google Scholar 

  3. World Anti-Doping Agency (2019) Anti-doping testing figure. https://www.wada-ama.org/sites/default/files/resources/files/2019_anti-doping_testing_figures_en.pdf. Accessed 18 Nov 2021

  4. Dmitrieva EV, Temerdashev AZ, Azaryan AA, Gashimova EM (2018) Determination of andarine (S-4), a selective androgen receptor modulator, and ibutamoren (MK-677), a nonpeptide growth hormone secretagogue, in urine by ultra-high performance liquid chromatography with tandem mass-spectrometric detection. J Anal Chem. https://doi.org/10.1134/S1061934818070031

    Article  Google Scholar 

  5. Narayanan R, Coss CC, Dalton JT (2018) Development of selective androgen receptor modulators (SARMs). Mol Cell Endocrinol. https://doi.org/10.1016/j.mce.2017.06.013

    Article  PubMed  Google Scholar 

  6. Zhang X, Sui Z (2013) Deciphering the selective androgen receptor modulators paradigm. Expert Opin Drug Discov. https://doi.org/10.1517/17460441.2013.741582

    Article  PubMed  Google Scholar 

  7. US Food and Drug Administration (2017) FDA warns against using SARMs in body-building products. https://www.fda.gov/news-events/fda-brief/fda-brief-fda-warns-against-using-sarms-body-building-products. Accessed 29 Oct 2021

  8. US Anti-Doping Agency (2015) Selective androgen receptor modulators (SARMs)—what athletes need to know. https://www.usada.org/spirit-of-sport/education/selective-androgen-receptor-modulators-sarms-prohibited-class-anabolic-agents/. Accessed 18 Nov 2021

  9. World Anti-Doping Agency (2021) World anti-doping code international standard prohibited list. https://www.wada-ama.org/sites/default/files/resources/files/2021list_en.pdf. Accessed 1 Jan 2021

  10. US Food and Drug Administration (2021) Dietary supplement ingredient advisory list. https://www.fda.gov/food/dietary-supplement-products-ingredients/dietary-supplement-ingredient-advisory-list. Accessed 23 Nov 2021

  11. US Food and Drug Administration (2017) Panther sports nutrition. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/panther-sports-nutrition-535341-10232017. Accessed 29 Oct 2021

  12. US Food and Drug Administration (2021) Former supplement company owner pleads guilty to unlawful distribution of steroid-like drugs. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/press-releases/former-supplement-company-owner-pleads-guilty-unlawful-distribution-steroid-drugs. Accessed 10 Feb 2021

  13. Food Safety Korea (2020) Hazardous food information. https://www.foodsafetykorea.go.kr/portal/board/boardDetail.do?menu_no=2806&bbs_no=bbs160119d&ntctxt_no=1078651&menu_grp=MENU_NEW02 (in Korean). Accessed 18 May 2021

  14. Temerdashev A, Dmitrieva E, Azaryan A, Gashimova E (2020) A novel approach to the quantification of urinary aryl-propionamide-derived SARMs by UHPLC–MS/MS. Biomed Chromatogr. https://doi.org/10.1002/bmc.4700

    Article  PubMed  Google Scholar 

  15. Thevis M, Geyer H, Kamber M, Schanzer W (2009) Detection of the aryl-propionamide-derived selective androgen receptor modulator (SARM) S-4 (Andarine) in a black-market product. Drug Test Anal. https://doi.org/10.1002/dta.91

    Article  PubMed  Google Scholar 

  16. Thevis M, Kohler M, Thomas A, Maurer J, Schloer N, Kamber M, Schänzer W (2008) Determination of benzimidazole- and bicyclic hydantoin-derived selective androgen receptor antagonists and agonists in human urine using LC–MS/MS. Anal Bioanal Chem. https://doi.org/10.1007/s00216-008-1882-6

    Article  PubMed  Google Scholar 

  17. Gadaj A, Ventura E, Healy J, Botre F, Sterk SS, Buckley T, Mooney MH (2020) Enhanced UHPLC-MS/MS screening of selective androgen receptor modulators following urine hydrolysis. MethodsX. https://doi.org/10.1016/j.mex.2020.100926

    Article  PubMed  PubMed Central  Google Scholar 

  18. Stacchini C, Botre F, Comunita F, De la Torre X, Dima AP, Ricci M, Mazzarino M (2021) Simultaneous detection of different chemical classes of selective androgen receptor modulators in urine by liquid chromatography-mass spectrometry-based techniques. J Pharmaceut Biomed. https://doi.org/10.1016/j.jpba.2020.113849

    Article  Google Scholar 

  19. Lee JH, Han JH, Jung EJ, Nallapaneni HK, Kim NS, Kim HI, Lee JK, Baek SY (2021) Development and validation of liquid chromatography-tandem mass spectrometry method for screening six selective androgen receptor modulators in dietary supplements. Food Addit Contam part A. https://doi.org/10.1080/19440049.2021.1906954

    Article  Google Scholar 

  20. Van Wagoner RM, Eichner A, Bhasin S, Deuster PA, Eichner D (2017) Chemical composition and labeling of substances marketed as selective androgen receptor modulators and sold via the internet. JAMA. https://doi.org/10.1001/jama.2017.17069

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ventura E, Gadaj A, Monteith G, Ripoche A, Healy J, Botre F, Saskia SS, Tom B, Mooney MH (2019) Development and validation of a semi-quantitative ultra-high performance liquid chromatography-tandem mass spectrometry method for screening of selective androgen receptor modulators in urine. J Chromatogr A. https://doi.org/10.1016/j.chroma.2019.04.050

    Article  PubMed  Google Scholar 

  22. Horwitz W, Chichilo P, Reynolds H (1970) Official methods of analysis of the association of official analytical chemists. Association of Official Analytical Chemists, Washington, DC

    Google Scholar 

  23. European Medicines Agency (2015) Harmonized tripartite guideline, validation of analytical procedures: text and methodology Q2(R1). International Conference on Harmonization. European Medicines Agency, London

  24. Jettanajit A, Nhujak T (2016) Determination of mycotoxins in brown rice using QuEChERS sample preparation and UHPLC–MS-MS. J Chromatogr Sci. https://doi.org/10.1093/chromsci/bmv244

    Article  PubMed  PubMed Central  Google Scholar 

  25. Moschou IC, Dasenaki ME, Thomaidis NS (2019) Ionization study and simultaneous determination of avermectins and milbemycines in fish tissue by LC-ESI-MS/MS. J Chromatogr B. https://doi.org/10.1016/j.jchromb.2018.11.017

    Article  Google Scholar 

  26. Dasenaki ME, Thomaidis NS (2015) Multi-residue determination of 115 veterinary drugs and pharmaceutical residues in milk powder, butter, fish tissue and eggs using liquid chromatography–tandem mass spectrometry. Anal Chim Acta. https://doi.org/10.1016/j.aca.2015.04.013

    Article  PubMed  Google Scholar 

  27. Thevis M, Schaner W (2016) Emerging drugs affecting skeletal muscle function and mitochondrial biogenesis–potential implications for sports drug testing programs. Rapid Commun Mass sp. https://doi.org/10.1002/rcm.7470

    Article  Google Scholar 

  28. Temerdashev AZ, Azaryan AA, Labutin AV, Dikunets MA, Zvereva IO, Podolskii II, Berodze GT, Balabaev IA (2017) Application of chromatography-mass spectrometry methods to the control of sport nutrition and medicines marketed via internet. J Anal Chem. https://doi.org/10.1134/S1061934817110090

    Article  Google Scholar 

  29. Kintz P, Ameline A, Gheddar L, Raul JS (2020) Testing for GW501516 (cardarine) in human hair using LC/MS-MS and confirmation by LC/HRMS. Drug Test Anal. https://doi.org/10.1002/dta.2802

    Article  PubMed  Google Scholar 

  30. Kintz P, Ameline A, Gheddar L, Raul JS (2019) LGD-4033, S-4 and MK-2866-testing for SARMs in hair: about 2 doping cases. Toxicol Anal Clin. https://doi.org/10.1016/j.toxac.2018.12.001

  31. Lee JH, Park HN, Choi JY, Kim NS, Park HY, Park SS, Baek SY (2017) Simultaneous analysis by quadrupole-orbitrap mass spectrometry and UHPLC-MS/MS for the determination of sedative-hypnotics and sleep inducers in adulterated products. J Sep Sci. https://doi.org/10.1002/jssc.201700879

    Article  PubMed  Google Scholar 

  32. Kim NS, Kim JH, Lim NY, Lee JH, Park SS, Kang HI (2020) Simultaneous determination of illegal drug substances in dietary supplements for gout and osteoporosis using ultra-performance liquid chromatography and liquid chromatography-quadrupole-time-of-flight mass spectrometry. J Pharm Biomed Anal. https://doi.org/10.1016/j.jpba.2019.113003

    Article  PubMed  Google Scholar 

  33. Kim NS, Lim NY, Kim CHS (2022) 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. Rapid Commun Mass sp. https://doi.org/10.1002/rcm.9275

    Article  Google Scholar 

  34. Thevis M, Piper T, Dib J, Lagojda A, Kuhne D, Packschies L, Geyer H, Schanzer W (2017) Mass spectrometric characterization of the selective androgen receptor modulator (SARM) YK-11 for doping control purposes. Rapid Commun Mass Spectrometry. https://doi.org/10.1002/rcm.7886

    Article  Google Scholar 

  35. Thevis M, Krug O, Geyer H, Schanzer W (2017) Expanding analytical options in sports drug testing: mass spectrometric detection of prohibited substances in exhaled breath. Rapid Commun Mass Spectrometry. https://doi.org/10.1002/rcm.7903

    Article  Google Scholar 

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Funding

This study was supported by a Grant [No. 21201MFDS306] of Ministry of Food and Drug Safety of Korea in 2021.

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Author notes

  1. Nam Sook Kim and Hwan Seong Choi have contributed equally to this article.

Authors and Affiliations

  1. Center for Advanced Analysis, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong Health Technology Administration Complex, 187 Osongsaengmyeong2-ro, Osongeup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, 363-700, Republic of Korea

    Nam Sook Kim, Hwan Seong Choi, Na Young Lim, Ji Hyun Lee, Hyungil Kim & Sun Young Baek

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  1. Nam Sook Kim
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  2. Hwan Seong Choi
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Correspondence to Sun Young Baek.

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Kim, N.S., Choi, H.S., Lim, N.Y. et al. Application of Simultaneous Analytical Methods for Selective Androgen Receptor Modulator Adulterated in Dietary Supplements Advertised as Muscle Strengthening Using UHPLC-PDA and LC–ESI–MS/MS. Chromatographia 85, 895–919 (2022). https://doi.org/10.1007/s10337-022-04170-y

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