ACP‐105 is a novel nonsteroidal selective androgen receptor modulator (SARM) with a tissue‐specific agonist effect and does not have side effects associated with the use of common androgens. This research reports a comprehensive study for the detection of ACP‐105 and its metabolites in racehorses after oral administration (in vivo) and postulating its structures using mass spectrometric techniques. To obtain the metabolic profile of ACP‐105, a selective and reliable LC‐MS/MS method was developed. The chemical structures of the metabolites were determined based on their fragmentation pattern, accurate mass, and retention time. Under the current experimental condition, a total of 19 metabolites were detected in ACP‐105 drug administered equine urine samples. The study results suggest the following: (1) ACP‐105 is prone to oxidation, which gives corresponding monohydroxylated, dihydroxylated, and trihydroxylated metabolites; (2) along with oxidation, there is a possibility of elimination of water molecule (dehydration) from the third position of the tropine moiety, resulting in the dehydrated analogs of corresponding monohydroxylated, dihydroxylated, and trihydroxylated metabolites; (3) from the study on the metabolites using LC‐MS/MS, it is clear that the fragmentation pattern is identical and a great number of fragment ions are common in all the metabolites and the parent drug. (4) The ACP‐105 and its metabolites were detected for up to 72 h; thus, the result is a valuable tool for evaluating its use and/or misuse in sport.

Since 2010, there has been an increasing number of adverse analytical findings related to selective androgen receptor modulators (SARMs) in competitive sports. It emphasizes the importance of comprehensive doping control analytical procedures that are capable of detecting SARM misuse.Methods: In this study, it is described how LY2452473, a SARM, was metabolized in thoroughbred horses after a single-dose oral administration and in vitro with equine liver microsome preparations. An investigation of the metabolism of LY2452473 in horses' urine, plasma, and hair matrices was carried out during the study. The plausible structures of the detected metabolites were postulated using highperformance liquid chromatography-high resolution mass spectrometry.Results: Under the experimental conditions 15 metabolites (12 phase I and three conjugates of phase I) were detected (M1-M15). The major phase I metabolites identified were formed by hydroxylation. Side-chain dissociated and methylated metabolites were also detected. In phase II, the glucuronic acid and sulfonic acid conjugates of hydroxy LY2452473 were detected as the major metabolites. In vitro analysis has confirmed the presence of all metabolites found in vivo except for the methylated analogs M11 and M12. A peak concentration of LY2452473 (0.5 pg/mg) in proximal hair segments was achieved 4 weeks after administration, according to hair analysis.Conclusions: Data obtained will aid in identifying LY2452473 and related substances faster. Furthermore, the results will assist in checking for the illegal use of these substances in competitive sports. | INTRODUCTIONThe role of androgens in male sexual development and maintenance cannot be overstated. 1 Androgens are predominant in male reproductive organs, but also moderately expressed in female genitalia and ovaries, as well as in skin, sebaceous glands, sweat glands, hair follicles, cardiac muscles, skeletal muscles, and brain. 2 A risk of serious side effects, such as prostate cancer development and progression, has limited the use of steroidal androgens. [3][4][5] Selective androgen receptor modulators (SARMs) are tissue-specific to anabolic target tissues (muscle and bone) and do not have the side effects associated with conventional androgens. The basic idea of the SARMs is that they modulate the transcriptional activity of the androgen receptor in a tissue-selective fashion. These compounds are agonistic in their effects on target tissues such as muscle and bone, but weak in their effects on reproductive organs (prostate). The molecular

Corticoids have found their way into the globe of sports, due to their anti-inflammatory properties, and have often found to be added to dietary supplements for illegally improving the effectiveness of their products. Earlier studies describe the detection of corticoids in several matrices, but this can be an incessant and continuous process as long because the doping practices continue. In this study, we report a technique to verify concurrently 44 of the foremost commonly abused synthetic corticoids (including chiral analogs) in equine plasma supported chiral liquid chromatography-electrospray ionization mass spectrometry. Polysaccharide i-cellulose-5 column was used for chromatographic separation with a gradient mode. The validation studies were also meted out by using equine plasma so as to judge the suitability of the strategy. Detection limits were determined between 0.01 and 0.05 ng/mL and therefore the limit of quantification was between 0.1 and 0.5 ng/mL. Recovery and matrix effect on the analytes was further assessed. Since the developed method was ready to separate the corticoids and to differentiate chiral analogs at very low levels (in picograms), this separation techniques may be employed for the determination (confirmatory analysis) of the corticoids in the forensic and anti-doping application.

Rationale: The formation of mass adducts is common during electrospray ionization mass spectrometry (ESI-MS). However, the mechanism that leads to adduct formation is poorly understood and difficult to control. Multiplication of mass adducts at once will adversely impact the sensitivity of mass analysis and cause misinterpretation of the level of detection. Prior studies on selective androgen receptor modulators (SARMs) revealed an immense mass adduct formation in both positive and negative ESI modes.Methods: In this study, additives in the mobile phases are investigated as a potential means of controlling mass adduct formation in various SARMs. Results:The first evidence of chloride adduct formation when SARMs are detected via ESI-MS has been reported in this research. A series of mobile phase combinations were tested to achieve the optimal condition for HPLC-MS. A comparison was also made between adduct formation on various grades of water used for preparing the mobile phase. A validation study using equine urine and plasma was also conducted to assess the suitability of the developed method. Conclusion:The results of this study will allow for a more accurate identification of SARMs, which will make it easier to investigate their illicit use in horse racing. | INTRODUCTIONIn mass spectrometers, molecule fragmentation is dependent on the stability of molecular ions. As a result, the fragmentation pattern of a molecule can be reproduced, and it contains valuable information about its chemical structure. The term adduct refers to a version of a

Nonsteroidal selective androgen receptor modulators (SARMs) are a novel class of compounds that have not yet been clinically approved; however, they appear to have a better anabolic/androgenic ratio than steroids and cause slighter side effects. Sports drug testing laboratories are required to maintain continuously updated doping control analytical methods in light of the widespread misuse of SARMs in elite and amateur sports. This paper describes the metabolic conversion of SARM GSK2881078 in thoroughbred horses following oral administration and in vitro with equine liver microsomes. A liquid chromatography-high-resolution mass spectrometry method was used to postulate the plausible structures of the detected metabolites. A total of five (M1-M5) in vivo metabolites and six (M1-M6) in vitro metabolites were detected under experimental conditions. Phase I metabolites mainly result from hydroxylation. Methoxylated and side-chain dissociated metabolites were also detected. Neither sulfonic acid nor glucuronic acid conjugated metabolites were observed in this study. Data reported here could aid in the detection of nonsteroidal SARM GSK2881078 and reveal its illicit use in competitive sports.