Selective androgen receptor modulators: comparative excretion study of bicalutamide in bovine urine and faeces

Abstract

Besides their development for therapeutic purposes, non-steroidal selective androgen receptor modulators (non-steroidal SARMs) are also known to impact growth-associated pathways as ligands of androgenic receptors (AR). They present a potential for abuse in sports and food-producing animals as an interesting alternative to anabolic androgenic steroids (AAS). These compounds are easily available and could therefore be (mis)used in livestock production as growth promoters. To prevent such practices, dedicated analytical strategies should be developed for specific and sensitive detection of these compounds in biological matrices. The present study focused on Bicalutamide, a non-steroidal SARM used in human treatment of non-metastatic prostate cancer because of its anti-androgenic activity exhibiting no anti-anabolic effects. To select the most appropriate matrix to be used for control purposes, different animal matrices (urine and faeces) have been investigated and SARM metabolism studied to highlight relevant metabolites of such treatments and establish associated detection time windows. The aim of this work was thus to compare the urinary and faecal eliminations of bicalutamide in a calf, and investigate phase I and II metabolites. The results in both matrices showed that bicalutamide was very rapidly and mainly excreted under its free form. The concentration levels were observed as higher in faeces (ppm) than urine (ppb); although both matrices were assessed as suitable for residue control. The metabolites found were consistent with hydroxylation (phase I reaction) combined or not with glucuronidation and sulfation (phase II reactions). Copyright © 2016 John Wiley & Sons, Ltd.

Development of a multi‐residue high‐throughput UHPLC–MS/MS method for routine monitoring of SARM compounds in equine and bovine blood

“…10 Whilst ideally both urine and blood should be sampled for antidoping and food safety control purposes, the extended window for detection of parent SARM compounds in feces has also been reported confirming that two SARM compounds with arylpropionamide pharmacophores (bicalutamide and ostarine (S-22)) are excreted in bovine feces. 11,12 However, the use of feces in routine testing remains restricted as it is neither a required matrix to be tested in the frame of EU residue control schemes nor is it authorized within antidoping programs. The advantages of blood-based analysis include the relative short duration required for on-demand sampling during training, prerace, or post-competition compared with that for urine collection.…”

“…Therefore, current efforts primarily remain focused on the development of analytical detection strategies utilizing urine and blood as test matrices of choice. Assays based on these complementary matrices rely on the detection of either parent compounds and/or respective metabolites 5,6,11,12,14 where compounds are rapidly metabolized, as is the case with many SARMs.…”

Investigation of stability of selective androgen receptor modulators in urine

“…Fair sport performances and foods free from SARM residue contamination can only be ensured through reliable and sensitive analytical methods which can detect SARMs in a range of biological matrices. Even if various analytical procedures have been developed and validated for the identification of SARM compounds in a range of matrices including urine (Ventura et al 2019), blood (Hansson et al 2016(Hansson et al , 2018, muscle (Gadaj et al 2019) and faeces (Cesbron et al 2017;Rojas et al 2017), there remains a consistent lack of information concerning the stability of SARM residues and matrix constituents during test sample storage. Stability is defined as the ability of material when stored under specific conditions to maintain a stated property (e.g.…”

Monitoring of selective androgen receptor modulators in bovine muscle tissue by ultra-high performance liquid chromatography-tandem mass spectrometry

“…To date, a number of LC-MS/MS applications have been reported with respect to the analysis of SARM residues in bovine species including urine (Beucher et al, 2017, Cesbron et al, 2017, de Rijke et al, 2013, Rojas et al, 2017, Schmidt and Mankertz, 2018, Ventura et al, 2019), blood (Ventura et al, 2018a, Ventura et al, 2018b) and faeces (Cesbron et al, 2017, Rojas et al, 2017) matrices, some of which have been validated in accordance with current regulatory legislation (EC, 2002a). However, in the case of surveillance at food retail level and for products imported into the EU, it is necessary to have methods applicable to the analysis of meat-based matrices.…”