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

Dmitrieva, Ekaterina; Темердашев, А. З.; Azaryan, A. A.; Gashimova, Elina

doi:10.1134/s1061934818070031

Cited by 9 publications

(6 citation statements)

References 16 publications

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“…The metabolism of MK‐0677 in humans has been investigated not only in vitro using pooled human liver microsomes but also in vivo following an oral administration of 10 mg of MK‐0677 to a healthy male volunteer 17 . Analytical methods have also been developed for the detection of MK‐0677 in human doping samples 18–20 . More recently, the equine metabolism has been investigated in vitro using equine liver microsomes, with a total of 20 phase I and 12 phase II metabolites that were detected 21 .…”

Section: Introductionmentioning

confidence: 99%

“…17 Analytical methods have also been developed for the detection of MK-0677 in human doping samples. [18][19][20] More recently, the equine metabolism has been investigated in vitro using equine liver microsomes, with a total of 20 phase I and 12 phase II metabolites that were detected. 21 Knowledge of species-specific metabolism profiles allows the refinement of screening targets in doping control.…”

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confidence: 99%

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Equine metabolism of the growth hormone secretagogue MK‐0677 in vitro and in urine and plasma following oral administration

Cutler

Viljanto²,

Taylor³

et al. 2022

Drug Testing and Analysis

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Ibutamoren mesylate, or MK‐0677, is an orally active, nonpeptide growth hormone secretagogue that has been developed to stimulate excretion of endogenous growth hormone. It has been evaluated for the treatment of a range of clinical conditions but is not available therapeutically. Nonetheless, MK‐0677 is widely available to purchase online, sold as ‘supplement’ products. The mode of action and relative ease of purchase make MK‐0677 a potential threat with regard to sports doping. The aim of this study was to investigate the metabolism of MK0677 in the horse following in vitro incubation and oral administration to two Thoroughbred racehorses, in order to identify the most appropriate analytical targets for doping control laboratories. Liquid chromatography high resolution mass spectrometry was used for metabolite identification, and subsequently, liquid chromatography–tandem mass spectrometry was used to generate full metabolite profiles for post‐administration urine and plasma samples. Fourteen phase I metabolites were identified in vitro; 13 of these were subsequently detected in urine and nine in plasma collected post‐administration, alongside the parent compound in both matrices. In both urine and plasma, the longest duration of detection was observed for an O‐dealkylated metabolite of MK‐0677, and therefore, this would be the best target for the detection of MK‐0677 administration. MK‐0677 and the O‐dealkylated metabolite were found to be excreted largely unconjugated in urine and plasma.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Equine metabolism of the growth hormone secretagogue MK‐0677 in vitro and in urine and plasma following oral administration

Cutler

Viljanto²,

Taylor³

et al. 2022

Drug Testing and Analysis

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“…Ibutamoren, also known as MK-677 (Figure 1), is one of the new compounds from the said class, which was discovered and developed by Merck. 11 Ibutamoren is a potent, long-acting, selective and orally active growth hormone secretagogue. 12,13 It is a non-peptide agonist of the ghrelin receptor and mimics the growth hormone-stimulating action of the endogenous hormone ghrelin.…”

Section: Introductionmentioning

confidence: 99%

Characterization of equine liver microsome‐generated metabolites of growth hormone secretagogue small molecule ibutamoren

Philip

Kal

Subhahar

et al. 2021

Rapid Comm Mass Spectrometry

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Interest in growth hormone secretagogues has intensified during the past several years based on capable, ever-widening investigational applications of recombinant growth hormone in animals and humans. Ibutamoren is a potent, long-acting, selective and orally active non-peptide growth hormone secretagogue, which has a great potential for abuse as a performance-enhancing agent in sports.Methods: To support drug metabolism and pharmacokinetic studies of chiral pharmaceuticals, it is necessary to combine the resolving power of high-performance liquid chromatography with the sensitivity of mass spectrometric techniques. This paper describes the metabolic conversion of ibutamoren using equine liver microsomes and metabolite characterization using a QExactive high-resolution mass spectrometer.Results: A total of 32 metabolites for ibutamoren (20 phase I and 12 phase II) were detected. The important findings of the current research are as follows: (1) the growth hormone secretagogue ibutamoren was prone to oxidation, resulting in corresponding hydroxylated metabolites; (2) in ibutamoren, the dissociation of the phenyl ring and 2-amino-2-methylpropanamide side chain was also observed; (3) the glucuronic acid conjugates of mono-, di-and trihydroxylated analogues were detected; and (4) no sulfonic acid conjugated metabolites were observed in this study of ibutamoren. Conclusions:The reported data help in the speedy detection of the growth hormone secretagogue ibutamoren and reveal its illegal use in competitive sports.

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“…This accomplishment is considered of potential clinical importance for increasing GH secretion in humans and of considerable scientific interest because these small organic chemical compounds, similar to small peptides, have been shown to express agonist activity rather than antagonist activity. Merck discovered and developed ibutamoren (MK‐0677) as one of the novel compounds from the said class 11 …”

Section: Introductionmentioning

confidence: 99%

“…Merck discovered and developed ibutamoren (MK-0677) as one of the novel compounds from the said class. 11 Ibutamoren is a potent, long-acting, active growth hormone secretagogue that can be taken orally. 12,13 This non-peptide agonist mimics the growth-hormone-stimulating effects of the endogenous hormone ghrelin.…”

Section: Introductionmentioning

confidence: 99%

Characterization of growth hormone secretagogue small molecule ibutamoren (MK‐0677) and its possible metabolites in thoroughbred horses for doping control

Philip

Kal

Subhahar

et al. 2022

Rapid Comm Mass Spectrometry

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Rationale It is important to remember that performance‐enhancing agents such as non‐peptide growth hormone secretagogues present a significant risk of abuse. Ibutamoren (MK‐0677) is a potent, long‐acting, selective non‐peptide growth hormone secretagogue that can be taken orally. Methods This study examines ibutamoren and its metabolites in thoroughbred horses after oral administration. Liquid chromatography/high‐resolution mass spectrometry was used to determine the probable structures of the detected metabolites. Results In this study, 22 metabolites of ibutamoren were identified (17 phase I and 5 phase II). Oxidation of ibutamoren leads to hydroxylated metabolites (mono and di). The study also detected dissociated side chains (benzyl group and 2‐amino‐2‐methylpropanamide) and hydrogenated metabolites. The glucuronic acid conjugated analogs of ibutamoren were detected during phase II of the study, but no sulfonic acid conjugated analogs were observed. The major metabolites can be detected up to 96 hours after a single dose, and ibutamoren can persist for up to 72 hours. Conclusions These findings will aid in the detection of ibutamoren and the detection of its illegal use in competitive sports.

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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

Cited by 9 publications

References 16 publications

Equine metabolism of the growth hormone secretagogue MK‐0677 in vitro and in urine and plasma following oral administration

Equine metabolism of the growth hormone secretagogue MK‐0677 in vitro and in urine and plasma following oral administration

Characterization of equine liver microsome‐generated metabolites of growth hormone secretagogue small molecule ibutamoren

Characterization of growth hormone secretagogue small molecule ibutamoren (MK‐0677) and its possible metabolites in thoroughbred horses for doping control

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