FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Drug testing and analysis2020; 13(2); 299-317; doi: 10.1002/dta.2918

Detection and identification of ACP-105 and its metabolites in equine urine using LC/MS/MS after oral administration.

Abstract: ACP-105 is a novel nonsteroidal selective androgen receptor modulator (SARM) with a tissue-specific agonist effect and does not have side effects associated with the use of common androgens. This research reports a comprehensive study for the detection of ACP-105 and its metabolites in racehorses after oral administration (in vivo) and postulating its structures using mass spectrometric techniques. To obtain the metabolic profile of ACP-105, a selective and reliable LC-MS/MS method was developed. The chemical structures of the metabolites were determined based on their fragmentation pattern, accurate mass, and retention time. Under the current experimental condition, a total of 19 metabolites were detected in ACP-105 drug administered equine urine samples. The study results suggest the following: (1) ACP-105 is prone to oxidation, which gives corresponding monohydroxylated, dihydroxylated, and trihydroxylated metabolites; (2) along with oxidation, there is a possibility of elimination of water molecule (dehydration) from the third position of the tropine moiety, resulting in the dehydrated analogs of corresponding monohydroxylated, dihydroxylated, and trihydroxylated metabolites; (3) from the study on the metabolites using LC-MS/MS, it is clear that the fragmentation pattern is identical and a great number of fragment ions are common in all the metabolites and the parent drug. (4) The ACP-105 and its metabolites were detected for up to 72 h; thus, the result is a valuable tool for evaluating its use and/or misuse in sport.
© 2020 John Wiley & Sons, Ltd.
Get Full Text
Publication Date: 2020-09-06 PubMed ID: 32852865DOI: 10.1002/dta.2918Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article is about a study on the detection and identification of ACP-105 and its metabolites in racehorse urine samples. The study used liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method to detect and establish the metabolic profile of ACP-105 and its possible impacts in sports.

Development of the LC-MS/MS Method

  • The researchers developed a reliable and selective LC-MS/MS method to obtain the metabolic profile of ACP-105, a novel nonsteroidal selective androgen receptor modulator (SARM).
  • They used this method to evaluate the fragmentation patterns, accurate mass, and retention time to determine the chemical structures of the metabolites found in the equine urine samples after the administration of ACP-105.

Findings

  • Under the experimental conditions of this study, a total of 19 metabolites were detected in the urine samples of horses after they were administered ACP-105.
  • One finding suggests that ACP-105 is prone to oxidation, resulting in various monohydroxylated, dihydroxylated, and trihydroxylated metabolites.
  • Along with oxidation, the researchers found that there is a possibility of dehydration from the third position of the tropine moiety. As a result, dehydrated analogs of the corresponding monohydroxylated, dihydroxylated, and trihydroxylated metabolites were produced.

Implications

  • One significant observation from the metabolite study via LC-MS/MS is that the fragmentation pattern is identical in all metabolites and the parent drug, with a great number of fragment ions shared between them.
  • Moreover, the detection of ACP-105 and its metabolites was possible for up to 72 hours after administration. This finding suggests that this method could be a valuable tool for evaluating potential use or misuse of ACP-105 in sports, especially since these substances have tissue-specific agonistic effects and do not trigger side-effects associated with common androgens.

Cite This Article

APA
Subhahar MB, Karakka Kal AK, Philip M, K Karatt T, N I, Vazhat RA, M P MA. (2020). Detection and identification of ACP-105 and its metabolites in equine urine using LC/MS/MS after oral administration. Drug Test Anal, 13(2), 299-317. https://doi.org/10.1002/dta.2918

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 13
Issue: 2
Pages: 299-317

Researcher Affiliations

Subhahar, Michael Benedict
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Karakka Kal, Abdul Khader
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Philip, Moses
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
K Karatt, Tajudheen
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
N, Ibrahimwaseem
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Vazhat, Ramees Abdulla
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
M P, Muhammed Ajeebsanu
  • Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.

MeSH Terms

  • Administration, Oral
  • Androgens / administration & dosage
  • Androgens / metabolism
  • Androgens / urine
  • Animals
  • Azabicyclo Compounds / administration & dosage
  • Azabicyclo Compounds / metabolism
  • Azabicyclo Compounds / urine
  • Chromatography, Liquid / methods
  • Doping in Sports
  • Female
  • Horses / urine
  • Male
  • Substance Abuse Detection / methods
  • Tandem Mass Spectrometry / methods

References

This article includes 23 references
  1. Mooradian AD, Morley JE, Korenman SG. Biological actions of androgens.. Endocr Rev 1987;8(1):1-28.
  2. Mangelsdorf DJ, Thummel C, Beato M. The nuclear receptor superfamily: the second decade.. Cell 1995;83(6):835-839.
  3. Sar M, Lubahn DB, French FS, Wilson EM. Immuno-histochemical localization of the androgen receptor in rat and human tissues.. Endocrinology 1990;127(6):3180-3186.
  4. Gao W, Bohl CE, Dalton JT. Chemistry and structural biology of androgen receptor.. Chem Rev 2005;105(9):3352-3370.
  5. Heinlein CA, Chang C. Androgen receptor in prostate cancer.. Endocr Rev 2004;25(2):276-308.
  6. Mohler ML, Bohl CE, Jones A. Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit.. J Med Chem 2009;52(12):3597-3617.
  7. Acevedo S, Gardell L, Bradley SR, Piu F, Raber J. Selective androgens receptor modulators antagonize apolipoprotein E4-induced cognitive impairments.. Lett Drug des Discovery 2008;5(4):271-276.
  8. Rosen J, Negro-Vilar A. Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile.. J Musculoskelet Neuronal Interact 2002;2:222-224.
  9. Yarrow JF, Conover CF, McCoy SC. 17-Hydroxyestra- 4, 9, 11-trien-3-one (trenbolone) exhibits tissue selective anabolic activity: effects on muscle, bone, adiposity, hemoglobin, and prostate.. Am J Physiol Endocrinol Metab 2011;300(4):E650-E660.
  10. Haendler B, Cleve A. Recent developments in antiandrogens and selective androgen receptor modulators.. Mol Cell Endocrinol 2012;352(1-2):79-91.
  11. Narayanan R, Mohler ML, Bohl CE, Miller DD, Dalton JT. Selective androgen receptor modulators in preclinical and clinical development.. Nucl Recept Signal 2008;6:1-26, E010.
  12. Allan G, Lai M, Sbriscia T. A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy-induced bone loss in rats.. J Steroid Biochem Mol Biol 2007;103(1):76-83.
  13. Gao W, Reiser P, Coss C. Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats.. Endocrinology 2005;146(11):4887-4897.
  14. Sun C, Robl J, Wang T. Discovery of potent, orally-active, and muscle-selective androgen receptor modulators based on an N-aryl-hydroxybicyclohydantoin scaffold.. J Med Chem 2006;49(26):7596-7599.
  15. Schlienger N, Lund BW, Pawlas J. Synthesis, structure-activity relationships, and characterization of novel non-steroidal and selective androgen receptor modulators.. J Med Chem 2009;52(22):7186-7191.
  16. Grata E, Perrenoud L, Saugy M, Baume N. SARM-S4 and metabolites detection in sports drug testing: a case report.. Forensic Sci Int 2011;213(1-3):104-108.
  17. Starcevic B, Ahrens BD, Butch AW. Detection of the selective androgen receptor modulator S-4 (andarine) in a doping control sample.. Drug Test Anal 2013;5(5):377-379.
  18. Kintz P, Ameline A, Gheddar L, Raul J. LGD-4033, S-4 and MK-2866-testing for SARMs in hair: about 2 doping cases.. Toxicologie Analy & Cliniq 2019;31(1):56-63.
  19. Beuck S, Schänzer W, Thevis M. Investigation of the in vitro metabolism of the emerging drug candidate S107 for doping-preventive purposes.. J Mass Spectrom 2011;46(2):112-130.
  20. Thevis M, Geyer H, Thomas A, Schänzer W. Trafficking of drug candidates relevant for sports drug testing: detection of non-approved therapeutics categorized as anabolic and gene doping agents in products distributed via the Internet.. Drug Test Anal 2011;3(5):331-336.
  21. Thevis M, Thomas A, Piper T, Krug O, Delahaut P, Schänzer W. Liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry based identification of in vivo generated metabolites of the selective androgen receptor modulator ACP-105 for doping control purposes.. Eur J Mass Spectrom 2014;20(1):73-83.
  22. Thevis M, Piper T, Beuck S, Geyer H, Schänzer W. Expanding sports drug testing assays: Mass spectrometric characterization of the selective androgen receptor modulator drug candidates RAD140 and ACP-105.. Rapid Commun Mass Spectrom 2013;27(11):1173-1182.
  23. Subhahar M, Singh J, Albert PH, Kadry AM. Pharmacokinetics, metabolism and excretion of celecoxib, a selective cyclooxygenase- 2 inhibitor, in horse.. J Vet Pharmacol Therap 2019;1-7.

Citations

This article has been cited 2 times.
  1. Broberg MN, Knych H, Bondesson U, Pettersson C, Stanley S, Thevis M, Hedeland M. Investigation of Equine In Vivo and In Vitro Derived Metabolites of the Selective Androgen Receptor Modulator (SARM) ACP-105 for Improved Doping Control. Metabolites 2021 Feb 1;11(2).
    doi: 10.3390/metabo11020085pubmed: 33535528google scholar: lookup
  2. Fijałkowska O, Jurowski K. Toxicity of ACP-105: a substance used as doping in sports: application of in silico methods for prediction of selected toxicological endpoints. Arch Toxicol 2025 Apr;99(4):1485-1503.
    doi: 10.1007/s00204-025-03962-zpubmed: 40064700google scholar: lookup
Subscribe to our newsletter
Join 99,658 horse owners like you who receive our email updates on horse health and nutrition.