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1.
Drug Test Anal ; 9(9): 1291-1303, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28087984

ABSTRACT

The artificial increase of the physical capability of horses using drugs is well known in racing and other equine sports. Both illicit and therapeutic substances are regarded as prohibited substances in competition in most countries. Some countries make distinctions for a few, specific drugs which are, however, allowed for use in other countries. The primary objective in the case of doping control is the detection of any trace of drug exposure, either parent drug or any of its metabolites, using the most powerful analytical methods which are generally based on chromatographic/mass spectrometric techniques. Of major concern in horseracing is the absence of a single organization regulating the anti-doping framework; instead of this, individual racing authorities provide rules and regulations often resulting in variations in the applied doping control programmes of different countries. The aim of this paper is to review the recent literature (approximately from 2012 to mid-2016) to highlight the numerous and diverse challenges faced in doping control of racing and equestrian sports, including the detection of designer drugs (anabolic steroids or stimulants) and of other emerging prohibited substances, such as peptides and noble gases in horse urine and plasma. Moreover, the application of 'omics' techniques (especially of metabolomics) deserves attention for establishing possible fingerprints of drug abuse as well as the evolution of instrumental analysis resulting a powerful ally in the fight against doping in equine sports. Copyright © 2017 John Wiley & Sons, Ltd.


Subject(s)
Body Fluids/chemistry , Designer Drugs/analysis , Doping in Sports/statistics & numerical data , Plasma/chemistry , Animals , Designer Drugs/chemistry , Environment , Horses , Metabolomics
2.
J Mass Spectrom ; 50(12): 1409-19, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26634976

ABSTRACT

This manuscript describes the direct detection of mesteroloe sulfo-conjugated metabolites by liquid chromatography/quadrupole/time of flight mass spectrometry (LC/Q/TOFMS) with special focus on evaluation of their retrospective detectability and their structure elucidation. A comparison of their long-term detectability, with the mesterolone main metabolite (1α-methyl-5α-androstan-3α-ol-17-one) excreted in glucuronide fraction and detected by gas chromatography/high resolution mass spectrometry (GC/HRMS), is also presented. Studies on mesterolone were performed with samples obtained from two excretion studies after single oral administration of Proviron© by healthy volunteers. Potential sulfate metabolites were detected in post administration samples after liquid-liquid extraction (LLE) with ethyl acetate and LC/TOFMS analysis, in negative mode. Twelve mesterolone sulfate metabolites from the first excretion study and nine from the second were subsequently confirmed by LC/Q/TOFMS. Finally, six mesterolone sulfate metabolites were considered important taking into account their abundance and long-term detectability, encoded as M1, M2, M4, M5, M6 and M7. The proposed mesterolone sulfate metabolites M1, M2, M4 and M5 (excreted as sulfates) have the same retrospectivity with the main mesterolone metabolite, excreted in glucuronide fraction. For metabolite characterization, LC fractionation was performed. The metabolites were identified and characterized by GC/MS, after solvolysis and derivatization. Combined mass spectra data from trimethyl-silyl (TMS), TMS-enolTMS and methoxime-TMS derivatives were taken into account for the characterization of these metabolites. It was concluded that M1 is 1α-methyl-5α-androstan-3ß-ol-17 one, M2 is 1α-methyl-5α-androstan-3α-ol-17 one, M4 is 1α-methyl-5a-androstan-3ß, 16z-diol-17-one, M5 is 1α-methyl-5α-androstan-17z,4ξ-diol-3one, M6 is 1α-methyl-5α-androstan-3z,6z-diol-17-one and M7 is 4z-hydroxy-1α-methyl-5α-androstan-3,17-dione.

3.
J Mass Spectrom ; 50(5): 740-8, 2015 May.
Article in English | MEDLINE | ID: mdl-26259657

ABSTRACT

Methenolone (17ß-hydroxy-1-methyl-5α-androst-1-en-3-one) misuse in doping control is commonly detected by monitoring the parent molecule and its metabolite (1-methylene-5α-androstan-3α-ol-17-one) excreted conjugated with glucuronic acid using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS) for the parent molecule, after hydrolysis with ß-glucuronidase. The aim of the present study was the evaluation of the sulfate fraction of methenolone metabolism by LC-high resolution (HR)MS and the estimation of the long-term detectability of its sulfate metabolites analyzed by liquid chromatography tandem mass spectrometry (LC-HRMSMS) compared with the current practice for the detection of methenolone misuse used by the anti-doping laboratories. Methenolone was administered to two healthy male volunteers, and urine samples were collected up to 12 and 26 days, respectively. Ethyl acetate extraction at weak alkaline pH was performed and then the sulfate conjugates were analyzed by LC-HRMS using electrospray ionization in negative mode searching for [M-H](-) ions corresponding to potential sulfate structures (comprising structure alterations such as hydroxylations, oxidations, reductions and combinations of them). Eight sulfate metabolites were finally detected, but four of them were considered important as the most abundant and long term detectable. LC clean up followed by solvolysis and GC/MS analysis of trimethylsilylated (TMS) derivatives reveal that the sulfate analogs of methenolone as well as of 1-methylene-5α-androstan-3α-ol-17-one, 3z-hydroxy-1ß-methyl-5α-androstan-17-one and 16ß-hydroxy-1-methyl-5α-androst-1-ene-3,17-dione were the major metabolites in the sulfate fraction. The results of the present study also document for the first time the methenolone sulfate as well as the 3z-hydroxy-1ß-methyl-5α-androstan-17-one sulfate as metabolites of methenolone in human urine. The time window for the detectability of methenolone sulfate metabolites by LC-HRMS is comparable with that of their hydrolyzed glucuronide analogs analyzed by GC-MS. The results of the study demonstrate the importance of sulfation as a phase II metabolic pathway for methenolone metabolism, proposing four metabolites as significant components of the sulfate fraction.


Subject(s)
Doping in Sports , Gas Chromatography-Mass Spectrometry/methods , Glucuronides/urine , Methenolone/urine , Sulfates/urine , Adult , Chromatography, Liquid/methods , Glucuronides/chemistry , Glucuronides/metabolism , Humans , Male , Methenolone/chemistry , Methenolone/metabolism , Middle Aged , Sulfates/chemistry , Sulfates/metabolism
4.
Clin Chim Acta ; 425: 242-58, 2013 Oct 21.
Article in English | MEDLINE | ID: mdl-23954776

ABSTRACT

Beta2-adrenergic agonists, or ß2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of ß2-agonists is prohibited in sports by the World Anti-Doping Agency (WADA) due to claimed anabolic effects, and also, is prohibited as growth promoters in cattle fattening in the European Union. This paper reviews the last seven-year (2006-2012) literature concerning the development of novel ß2-agonists molecules either by modifying the molecule of known ß2-agonists or by introducing moieties producing indole-, adamantyl- or phenyl urea derivatives. New emerging ß2-agonists molecules for future therapeutic use are also presented, intending to emphasize their potential use for doping purposes or as growth promoters in the near future.


Subject(s)
Adrenergic beta-2 Receptor Agonists/isolation & purification , Anti-Inflammatory Agents/isolation & purification , Designer Drugs/isolation & purification , Dietary Supplements , Doping in Sports/prevention & control , Adrenergic beta-2 Receptor Agonists/chemical synthesis , Adrenergic beta-2 Receptor Agonists/therapeutic use , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/therapeutic use , Asthma/drug therapy , Cattle , Designer Drugs/chemical synthesis , Ethanolamines/chemical synthesis , Ethanolamines/isolation & purification , Growth Substances/chemical synthesis , Growth Substances/isolation & purification , Humans , Indoles/chemical synthesis , Indoles/isolation & purification , Quinolones/chemical synthesis , Quinolones/isolation & purification , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/isolation & purification
5.
J Chromatogr A ; 1256: 232-9, 2012 Sep 21.
Article in English | MEDLINE | ID: mdl-22901297

ABSTRACT

The comparison among different modelling techniques, such as multiple linear regression, partial least squares and artificial neural networks, has been performed in order to construct and evaluate models for prediction of gas chromatographic relative retention times of trimethylsilylated anabolic androgenic steroids. The performance of the quantitative structure-retention relationship study, using the multiple linear regression and partial least squares techniques, has been previously conducted. In the present study, artificial neural networks models were constructed and used for the prediction of relative retention times of anabolic androgenic steroids, while their efficiency is compared with that of the models derived from the multiple linear regression and partial least squares techniques. For overall ranking of the models, a novel procedure [Trends Anal. Chem. 29 (2010) 101-109] based on sum of ranking differences was applied, which permits the best model to be selected. The suggested models are considered useful for the estimation of relative retention times of designer steroids for which no analytical data are available.


Subject(s)
Anabolic Agents/analysis , Chromatography, Gas/methods , Neural Networks, Computer , Steroids/analysis , Trimethylsilyl Compounds/chemistry , Least-Squares Analysis
6.
J Chromatogr A ; 1216(47): 8404-20, 2009 Nov 20.
Article in English | MEDLINE | ID: mdl-19836752

ABSTRACT

A quantitative structure-retention relationship (QSRR) study has been performed to correlate relative retention times (RRTs) of trimethylsilylated (TMS) anabolic androgenic steroids (AAS) with their molecular characteristics, encoded by the respective descriptors, for the prediction of RRTs of novel molecules, using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). The elucidation of similarities and dissimilarities among the data structures was carried out using principal component analysis (PCA). Successful models were established using multiple linear regression (MLR) and partial least squares (PLS) techniques as a function of topological, three-dimensional (3D) and physicochemical descriptors. The models are useful for the estimation of RRTs of designer steroids for which no analytical data is available.


Subject(s)
Anabolic Agents/analysis , Androstenols/analysis , Gas Chromatography-Mass Spectrometry/methods , Designer Drugs , Doping in Sports , Least-Squares Analysis , Linear Models , Principal Component Analysis , Quantitative Structure-Activity Relationship , Trimethylsilyl Compounds/analysis
7.
J Steroid Biochem Mol Biol ; 115(1-2): 44-61, 2009 May.
Article in English | MEDLINE | ID: mdl-19429460

ABSTRACT

Unified metabolism schemes of anabolic androgenic steroids (AAS) in human urine based on structure classification of parent molecules are presented in this paper. Principal components analysis (PCA) was applied to AAS molecules referred in the World Anti-Doping Agency (WADA) list of prohibited substances, resulting to their classification into six distinct groups related to structure features where metabolic alterations usually occur. The metabolites of the steroids participating to these six groups were treated using the Excel(c) classification filters showing that common metabolism routes are derived for each of the above PCA classes, leading to the proposed metabolism schemes of the present study. This rule-based approach is proposed for the prediction of the metabolism of unknown, chemically modified steroids, otherwise named as designer steroids. The metabolites of three known, in the literature, AAS are estimated using the proposed metabolism schemes, confirming that their use could be a useful tool for the prediction of metabolic pathways of unknown AAS.


Subject(s)
Anabolic Agents/urine , Androgens/urine , Principal Component Analysis/methods , Substance Abuse Detection/methods , Anabolic Agents/metabolism , Androgens/metabolism , Designer Drugs , Doping in Sports , Humans , Metabolism , Steroids/urine
8.
Steroids ; 74(2): 172-97, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19028512

ABSTRACT

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone introduced for therapeutic purposes providing enhanced anabolic potency with reduced androgenic effects. Androgens mediate their action through their binding to the androgen receptor (AR) which is mainly expressed in androgen target tissues, such as the prostate, skeletal muscle, liver and central nervous system. This paper reviews some of the wide spectrum of testosterone and synthetic AAS structure modifications related to the intended enhancement in anabolic activity. The structural features of steroids necessary for effective binding to the AR and those which contribute to the stipulation of the androgenic and anabolic activities are also presented.


Subject(s)
Anabolic Agents/chemistry , Anabolic Agents/metabolism , Androgens/chemistry , Androgens/metabolism , Receptors, Androgen/metabolism , Steroids/chemistry , Steroids/metabolism , Animals , Humans , Protein Binding
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