Drug Testing and Analysis最新文献

The use of testosterone in racehorses is predominantly monitored using international urine and plasma concentration-based thresholds and complementary steroid ratios. To date, there has been no published pharmacokinetic study on transdermally applied testosterone products in horses and whether their use could result in adverse analytical findings. Therefore, quantitative analysis of testosterone and epitestosterone in urine and testosterone in plasma samples was performed following a pilot multi-dose transdermal Testogel administration (1 mg/kg once a day for 7 days on clipped skin) to one gelding and one mare. The peak concentrations (C_max) of free testosterone were 1060 and 1800 pg/mL in gelding and mare plasma, respectively. Testosterone concentrations exceeded the international plasma threshold of 100 pg/mL consistently for up to 4 h post-administration, after which detection above the threshold was sporadic up to 127 h. In urine, C_max of free and conjugated (sulfate and glucuronide) testosterone were 700 and 323 ng/mL in gelding and mare urine, respectively. In the gelding, testosterone concentrations exceeded the international urine threshold of 20 ng/mL consistently for up to 47 h post-administration, but sporadically up to 143 h. In all samples, testosterone: epitestosterone ratios were greater than 5, another requirement for adverse analytical findings in geldings. In the mare, testosterone concentrations exceeded the urine threshold of 55 ng/mL consistently for up to 71 h post-administration, but sporadically up to 167 h. Therefore, these limited results for one gelding and one mare demonstrate that doping control following transdermal applications of testosterone to racehorses is possible using existing approaches.

In an effort to conduct a desoxymethyltestosterone (DMT) administration study to replenish excretion urine inventory of Beijing Anti-Doping Laboratory for quality assurance purpose, a product labeled as “Pheraplex” was purchased from the internet. The product's label indicated that each capsule contained 10 mg of 17α-methyl-etioallocholan-2-ene-17β-ol (DMT), along with medicinal corn starch and gelatin. To verify the product's contents, gas chromatography tandem quadrupole mass spectrometry (GC–MS/MS) was employed to analyze the active ingredient and compare it with the reference materials of DMT. Surprisingly, the results revealed that the product did not contain DMT or any other steroids monitored in the initial testing procedure of our laboratory. Subsequently, nuclear magnetic resonance was utilized to identify the compound's structure, which was determined to be 17,17-dimethyl-18-nor-5α-androst-13-en-3β-ol. This compound was referred to as M10 of 17α-methyltestosterone in a literature. This finding highlights the potential discrepancies between product labeling and actual contents in the supplement market, which deserves attention from the anti-doping community.

Synthetic urine mimicking normal urine is difficult detectable by standard specimen validity testing. In this study, the VDx True Urine LD Test and True Urine SD Test, analysing ‘long duration’ (LD) and ‘short duration’ (SD) markers, were evaluated for their ability to detect synthetic urine. Two synthetic urines from the US market and 1188 real-life urine specimens were analysed for LD markers, SD markers, uric acid and temperature. Forty-seven specimens (set 1) showed uric acid and/or temperature suspicious results and were analysed by LC–MS/MS for 10 endogenous biomolecules. Diagnostic sensitivities and specificities were calculated for LD and SD markers based on uric acid and LC–MS/MS results of set 1. The false-positive rate of the SD marker was further evaluated with uric acid results of the other 1141 specimens (set 2). Additionally, direct synthetic urine markers were analysed by LC-(HR)MS. Uric acid and LC–MS/MS could identify synthetic urine. In one US synthetic urine, low concentrations of uric acid were found. Specimens of the Austrian/German region were reliably classified congruently by both methods. The LD and the SD markers detected both synthetic urines. For set 1, the LD had 100% sensitivity and 88.9% specificity, and the SD had 84.2% sensitivity and 44.4% specificity for authentic/synthetic specimens. In set 2, the SD marker specificity depended on the upper limit of the acceptance criteria. In one US synthetic urine, carbendazim was identified. Overall, several tests should be applied to confirm authentic or synthetic urine. Especially, simultaneous analysis of indirect and direct synthetic urine markers should be considered.

Ranitidine is a histamine H₂-receptor antagonist commonly used to treat gastric ulceration in horses. The author's laboratory conducted a study some years ago in the early 2000s on its metabolism as well as its urinary elimination profile in two geldings. With the technology advancement as well as popularity of blood for doping control testing, the laboratory has recently conducted another administration trials of the substance in six horses to study the in vivo metabolism of ranitidine, aiming to identify and reinvestigate the appropriate target(s) for controlling misuse of ranitidine in horses as well as to study its elimination in blood. To study the elimination and biotransformation of ranitidine, administration experiments were performed by giving six castrated horses (geldings) each 25 mL of Ulcerguard oral paste (equivalent to 9.8 g of ranitidine) in the morning and 20 mL of oral paste (equivalent to 7.9 g of ranitidine) in the afternoon daily for eight consecutive days. The postulated in vivo metabolites included ranitidine-S-oxide (M1), ranitidine-N-oxide (M2), desmethylranitidine (M3a/b) and furoic acid analogue of ranitidine (M4), resulting from oxidation, demethylation and oxidative deamination of ranitidine. To control the misuse of ranitidine in horses, elimination profiles of urinary and plasma ranitidine were established. Free ranitidine was detectable for at most 8 days and 72 h in urine and plasma, respectively. Both metabolites ranitidine-S-oxide and ranitidine-N-oxide were detected for 8 days, and therefore, they could be monitored alongside the parent drug as evidence that the substance has gone through the horse's body.

Previously, we used ecological momentary assessment (EMA) to evaluate motivations and temporal patterns of kratom use for 15 days among US adult kratom consumers (N = 357). Here we present the content analyses of the products used during that nationwide study, with quantification of 10 kratom alkaloids. The samples (N = 341) were primarily whole-leaf products, not extracts, and were similar to each other in their alkaloid composition, closely matching the chromatographic-mass spectrometry fingerprint expected for Mitragyna speciosa leaf material. We found no evidence of adulteration with illicit or prescription drugs. With participants' self-reported data on kratom amount per use, we calculated mitragynine intake per use: mean 31.3 mg and median 25.4 mg (range 2.0–205.9 mg). With self-reported data on frequency, we calculated mitragynine intake per day, it ranged from 78.3 to 134.6 mg (mean) or 50.8 to 101.6 mg (median). This is the most comprehensive analysis of US whole-leaf kratom products to date. The coupling of self-report and product sample-analysis data to quantify daily alkaloid intake is foundational for designing controlled clinical trials of kratom in healthy volunteers. These findings on kratom products' chemical composition and daily kratom alkaloid consumption can also inform clinicians, policymakers, and consumers, particularly for whole-leaf material.

Hair testing is a very effective method for drug use investigation. The finding of drugs of abuse in children hair may reflect environmental exposure, accidental ingestion, passive inhalation, intentional administration, and, in case of neonates and infants, in-utero and breast exposure. Despite its increasing use, interpretation of children hair analysis remains difficult, cut-off values used in adults cannot be applied, and no reference ranges for different age groups currently exist. To contribute to the identification of a reference framework for hair analysis in children and adolescents, a comparison of data gathered from different geographical areas could be useful. With this view, this study shows the results of hair analysis of children and adolescents who underwent testing for clinical purposes in a hospital setting in north-east Italy. Cocaine represents the most frequently detected drug in all age groups (overall, 94 positives). The highest number and ratio of cocaine positivity was found among children aged 1–3 years (21 out of 32 children; 65.6%) and the highest concentration among infants within 1 year. The results suggest that exposure to drugs of abuse represents a nonnegligible problem particularly in infants and toddlers, which requires special attention in clinical and social setting. In view of the multiple possible ways of exposure, it is essential to perform a case-by-case evaluation and to collect as much information as possible to frame the case and to implement the most effective child protection measures.