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During the Belle Epoque, the use of cocaine, well known to the South American populations, spread among the European elite in the form of a tonic drink created from coca leaves macerated in Bordeaux wine, the Mariani wine. Nowadays, bottles in circulation are extremely rare but the investigations of a Parisian historian led him to the discovery of a bottle of wine that belonged to Angelo Mariani's estate at the end of the 19th century. Our laboratory was asked to analyse the contents of the bottle in order to search for the main active compounds and to estimate the state of preservation. The analysis of the centenarian product collected was aimed at identifying the alcohols and solvents by HS-GC/FID and HS-GC/MS after dilution in water, and the main alkaloids contained in all the samples by LC-HRMS screening and LC-MS/MS quantification. The Mariani wine presented an alcohol content of 15.7°. The screening and the subsequent dosage revealed the following substances: cocaine (86 ng/mL), benzoylecgonine (383 ng/mL), cocaethylene (17 ng/mL), ecgonine methyl ester (130 ng/mL), caffeine, cuscohygrine, cinnamoylcocaine and synephrine. The alkaloids found in the Mariani wine confirm the real presence of coca leaves in this drink. Their low concentrations may indicate drug instability. The presence of cocaethylene demonstrates that it can be formed without passing through the liver, which was supposed to be the site of production when cocaine and ethanol are present in the body at the same time. These appear to be the first report in the literature presenting the analysis of Mariani wine with the dosage of cocaine derivatives. • First analysis of a 19th century bottle of Mariani wine using MS technologies. • Determination of the real presence of cocaine and metabolites in Mariani wine. • Evidence of the presence of cocaethylene formed outside the liver system. [ABSTRACT FROM AUTHOR]

The selective androgen receptor modulators are a recent class of anabolic agents, used to improve athletic performance. Among these molecules, there is (2 S)-N-(4-cyano-3-trifluoromethylphenyl)− 3-(3-fluoro-4-chlorophenoxyl)2-hydroxy-2-methyl-propanamide, commonly known as S-23. This molecule appeared very recently on the doping market. As a result, very few data are available in the literature, and nothing has been published about long-term effects of S-23. The authors focused on the detection of S-23 and its metabolites in human urine, following a single oral administration of approx. 8 mg to a volunteer, using standard ultra-performance liquid chromatography-triple quadrupole-mass spectrometry (UPLC-MS/MS), and ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UPLC-Q-TOF-MS). To the best of the authors knowledge, this seems to be the first study ever achieved on S-23. In vitro experiment was performed, using human liver microsomes, in order to investigate the potential CYP- and UGT-dependent S-23 metabolites. Four metabolites were produced, which were identified as hydroxy-S-23 (C 18 H 12 O 4 N 2 ClF 4 : m/z [M-H-] 431.0423); O -dephenylate-S-23 (C 12 H 10 O 3 N 2 F 3 : m/z [M-H-] 287.0647); S-23-glucuronide (C 24 H 20 O 9 N 2 ClF 4 : m/z [M-H-] 591.0794) and hydroxy-S-23-glucuronide (C 24 H 20 O 10 N 2 ClF 4 : m/z [M-H-] 607.0743). After consumption of S-23, the parent drug was detectable in hydrolyzed urine from 2 h post administration up to 28 days, with concentrations ranging between 0.5 and 93 ng/mL. In the urine, only one of the four metabolites identified in vitro was detected, hydroxy-S-23. This metabolite was detected up to 28 days. It does not seem to increase the window of detection of S-23 as the ratio between hydroxy-S-23 and the parent drug was always lower than 1. Another metabolite, dihydroxy-S-23, not identified in vitro, was identified in the urine of the volunteer. Hair sample, collected one month after the consumption of a single tablet, was negative for S-23 and hydroxy-S-23, with a LOQ at 0.1 pg/mg. [Display omitted] • The authors focused on the detection of S-23 and its metabolites in human urine, following a oral administration of 8 mg. • Four metabolites were produced in vitro, using human liver microsomes. • Parent S-23 was detectable in hydrolyzed urine up to 28 days. • Hydroxy-S-23 was detected up to 28 days, in urine. Dihydroxy-S-23 was detected from + 8 hours up to 5 days. • Hair sample, collected one month after the exposure, was negative for S-23 and metabolites, with a LOQ at 0.1 pg/mg. [ABSTRACT FROM AUTHOR]

Clomiphene is a selective estrogen receptor modulator. It is indicated for the treatment of female infertility issues but in sport, it can be misused to stimulate endogenous testosterone secretion in men. Therefore, it has been prohibited at all times by the World Anti-doping Agency. The aim of this study was to get data to be able to interpret concentrations in athletes. A healthy volunteer (male, 62 years-old) ingested a single therapeutic dose of clomiphene (Clomid™, 50 mg). Strands of hair (blond, 4 cm) were collected one month after the ingestion. Body hair (beard, axillary, pubic and chest hair), and finger and toenails were collected over 4–5 months. A previous method was modified to identify and quantify clomiphene in keratinous matrices. 30 mg of specimen were sonicated and incubated in 1 mL of methanol, in presence of 200 pg of clomiphene-D 5 (internal standard). After centrifugation and evaporation of the organic phase, the samples were analyzed using LC-MS/MS. Linearity was verified in hair and nail clippings between 1 and 500 pg/mg. The limits of detection and quantification were determined at 0.3 and 1 pg/mg respectively. The study demonstrated that clomiphene tested positive in all the analyzed specimens at 9 pg/mg in head hair, from 28 to 486 pg/mg (body hair) and from 4 to 57 pg/mg (nails). Clomiphene was identified for the first time in multiple keratinous matrices. This study demonstrated that a single oral therapeutic dose is detectable in keratinous matrices over a long period of time. • A single dose of clomiphene (50 mg) is detectable in head hair, body hair and nail clippings. • A single therapeutic dose is detectable for a long period in keratinous matrices. • Higher concentrations of clomiphene are identified in body hair than in head hair. [ABSTRACT FROM AUTHOR]