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Metabolic studies of selective androgen receptor modulators RAD140 and S‐23 in horses
Author(s) -
So YatMing,
Wong Jenny K. Y.,
Choi Timmy L. S.,
Prabhu Anil,
Stewart Brian,
Farrington Adrian F.,
Robinson Paul,
Wan Terence S. M.,
Ho Emmie N. M.
Publication year - 2021
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.2920
Subject(s) - glucuronidation , metabolite , sulfation , chemistry , glucuronide , biotransformation , metabolic pathway , in vitro , in vivo , s9 fraction , urine , hydroxylation , pharmacology , chromatography , metabolism , glucuronic acid , androgen receptor , biochemistry , microsome , medicine , biology , enzyme , polysaccharide , microbiology and biotechnology , prostate cancer , cancer
This paper describes the studies of the in vitro biotransformation of two selective androgen receptor modulators (SARMs), namely, RAD140 and S‐23, and the in vivo metabolism of RAD140 in horses using ultra‐high performance liquid chromatography–high resolution mass spectrometry. in vitro metabolic studies of RAD140 and S‐23 were performed using homogenised horse liver. The more prominent in vitro biotransformation pathways for RAD140 included hydrolysis, hydroxylation, glucuronidation and sulfation. Metabolic pathways for S‐23 were similar to those for other arylpropionamide‐based SARMs. The administration study of RAD140 was carried out using three retired thoroughbred geldings. RAD140 and the majority of the identified in vitro metabolites were detected in post‐administration urine samples. For controlling the misuse of RAD140 in horses, RAD140 and its metabolite in sulfate form gave the longest detection time in hydrolysed urine and could be detected for up to 6 days post‐administration. In plasma, RAD140 itself gave the longest detection time of up to 13 days. Apart from RAD140 glucuronide, the metabolites of RAD140 described herein have never been reported before.