Detection of the selective androgen receptor modulator GSK2881078 and metabolites in urine and hair after single oral administration

Abstract

Hair and urine concentrations of the nonsteroidal selective androgen receptor modulator GSK2881078 were examined following single oral administration to investigate its hair incorporation and estimate the general suitability of hair testing for selected androgen receptor modulators. Hair segments were collected following a single dose of 1.5 mg GSK2881078 by repeated shaving of scalp hair at Week 0 (blank), Week 1 (representing the pre-application period), Week 3 (ideally focusing the time of incorporation), and Weeks 5 and 9 (post-administration period). The intact compound and various (at least 4) hydroxy-metabolites exhibited similar elimination profiles. The peak urinary concentration (approximately 920 pg/ml) was observed after 8 h and is reduced to the detection limit (2 pg/ml) on Day 42 following administration of 760 μg GSK2881078. Correspondingly, hair concentrations of GSK2881078 (intact compound only) following a single oral dose of 1.5 mg GSK2881078 reached a peak concentration of 1.7 pg/mg in the segments collected 3 weeks post administration, representing the time of ingestion. The concentration rapidly declined to trace amounts of 0.7 (Week 5) and 0.2 pg/mg (Week 9), respectively. In conclusion, measurement of the intact compound GSK2881078 is feasible for both urine and hair analysis. However, concentrations in hair after single oral administration are in the low pg/mg range and can only be detected, if the segments cover the administration period.

Identification of equine in vitro metabolites of seven non‐steroidal selective androgen receptor modulators for doping control purposes

“…As a comparison, four mono‐hydroxylated metabolites of GSK2881078 were identified in human urine following an oral administration 34 . Three of the identified metabolites were postulated to be hydroxylated at the indole ring, with the fourth hydroxylated at the side chain.…”

“…This As a comparison, four mono-hydroxylated metabolites of GSK2881078 were identified in human urine following an oral administration. 34 Three of the identified metabolites were postulated to be hydroxylated at the indole ring, with the fourth hydroxylated at the side chain. No phase II metabolites were detected, suggesting that further biotransformation was not required for excretion of this compound.…”

“…GSK2881078 ((R)‐1‐(1‐(methylsulfonyl)propan‐2‐yl)‐4‐(trifluoromethyl)‐1 H ‐indole‐5‐carbonitrile) is an indole‐carbonitrile based SARM that has been shown to be well tolerated in elderly men and women, yielding dose‐dependent increases in lean mass 32,33 . Its metabolism has recently been investigated in the human following an oral administration, 34 but no equine metabolism information was available at the time of writing.…”

Perspectives in Evaluating Selective Androgen Receptor Modulators in Human Hair: A Short Communication

“…This is probably attributed to the current limited scientific interest in hair testing for drugs; however, one can anticipate a rapid growth in focus owing to the expansion of SARMs. In the last weeks, Rading et al 13 have identified GSK2881078, another SARM, in the hair of a subject after a single oral administration of 1.5 mg. The measured hair concentration, 3 weeks postadministration, was 1.7 pg/mg, confirming that a single exposure can be detected in human hair.…”

Peroxisome Proliferator-Activated Receptor Delta Agonist (PPAR- δ) and Selective Androgen Receptor Modulator (SARM) Abuse: Clinical, Analytical and Biological Data in a Case Involving a Poisonous Combination of GW1516 (Cardarine) and MK2866 (Ostarine)

“…It must be acknowledged that a single exposure to SARMs is not detectable in hair [ 9 ], except for GSK2881078 [ 31 ]. There is no data about GW1516 detection after a single exposure.…”