TY - JOUR
T1 - Equine in vivo metabolite profiling of the selective androgen receptor modulator LGD-3303 for doping control
AU - Broberg, Malin Nilsson
AU - Knych, Heather
AU - Bondesson, Ulf
AU - Pettersson, Curt
AU - Tidstedt, Börje
AU - Stanley, Scott
AU - Thevis, Mario
AU - Hedeland, Mikael
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/9/5
Y1 - 2023/9/5
N2 - LGD-3303 is a Selective Androgen Receptor Modulator (SARM) that is prohibited in both equine and human sports due to its anabolic properties. The aim of this study was to investigate the equine in vivo metabolite profile of LGD-3303 and identify drug metabolites that can be suitable as new and improved analytical targets for equine doping control. This was performed by an oral administration of 0.05 mg·kg−1 LGD-3303 to horses, where blood and urine samples were collected up to 96 h after administration. The in vivo samples consisting of plasma, urine and hydrolyzed urine were analyzed utilizing ultra-high performance liquid chromatography hyphenated to a Q Exactive™ Orbitrap™ high resolution mass spectrometer with a heated electrospray ionization source. A total of eight metabolites of LGD-3303 were tentatively identified, including one carboxylated and several hydroxylated metabolites in combination with glucuronic acid conjugates. A monohydroxylated metabolite is suggested as an analytical target for doping control analysis of plasma and urine after hydrolysis with β-glucuronidase, due to the high intensity and prolonged detection time in comparison to parent LGD-3303.
AB - LGD-3303 is a Selective Androgen Receptor Modulator (SARM) that is prohibited in both equine and human sports due to its anabolic properties. The aim of this study was to investigate the equine in vivo metabolite profile of LGD-3303 and identify drug metabolites that can be suitable as new and improved analytical targets for equine doping control. This was performed by an oral administration of 0.05 mg·kg−1 LGD-3303 to horses, where blood and urine samples were collected up to 96 h after administration. The in vivo samples consisting of plasma, urine and hydrolyzed urine were analyzed utilizing ultra-high performance liquid chromatography hyphenated to a Q Exactive™ Orbitrap™ high resolution mass spectrometer with a heated electrospray ionization source. A total of eight metabolites of LGD-3303 were tentatively identified, including one carboxylated and several hydroxylated metabolites in combination with glucuronic acid conjugates. A monohydroxylated metabolite is suggested as an analytical target for doping control analysis of plasma and urine after hydrolysis with β-glucuronidase, due to the high intensity and prolonged detection time in comparison to parent LGD-3303.
KW - Doping control
KW - Equine
KW - LGD-3303
KW - Mass spectrometry
KW - Metabolites
KW - Selective androgen receptor modulator
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U2 - 10.1016/j.jpba.2023.115468
DO - 10.1016/j.jpba.2023.115468
M3 - Article
C2 - 37224728
AN - SCOPUS:85160089615
SN - 0731-7085
VL - 233
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
M1 - 115468
ER -