Drug Testing and Analysis最新文献

The use of transdermal patches, primarily for pain relief, has grown significantly in recent years. This increase in legitimate use has been accompanied by a rise in their illegal use. Consequently, forensic laboratories are facing a growing number of these complex samples requiring analysis. These systems often involve complex sample matrices, demanding analytical techniques that are both efficient and highly sensitive. This study introduces the application of QuickProbe GC-MS for the rapid identification of fentanyl and buprenorphine in transdermal patches. Utilizing in situ extraction, the method eliminates the need for time-consuming sample preparation, achieving a full analysis cycle time of under 2 min. QP GC-MS successfully detected fentanyl and buprenorphine at concentrations as low as 4.125 and 5 mg, respectively, while adhering to the highest selectivity guidelines. This rapid and streamlined approach has broader implications for forensic investigations, enabling high-throughput screening of seized drug samples and potentially extending to the analysis of emerging drugs of abuse. The speed and efficiency of QP GC-MS make it a valuable tool for law enforcement, public health agencies, and toxicology labs facing the challenge of keeping pace with evolving drug trends.

Several studies have described the sedative effects of dimenhydrinate (DMH), although others report a stimulant effect on psychomotor functions. Because the first generation of antihistamines was shown to seriously impair cognitive psychomotor and driving performance in healthy volunteers, the aim of our research was to determine the effect of DMH by testing physical activity and cognitive and cardiovascular functions using an animal model to identify a possible stimulatory effect. The study protocol consisted of two phases. The first was designed to analyze the stimulating motor effect of DMH. Four study groups were formed: (1) vehicle (Veh), (2) modafinil (MOD), (3) DMH at 50 mg/kg (DMH-50), and (4) DMH at 200 mg/kg (DMH-200). Motor coordination and balance, physical activity, hemodynamics, and nitrous oxide (NO) quantification were performed. In the second phase, we sought to discriminate the compound in DMH that generates the stimulating effect. In this case, the study groups were (1) Veh, (2) MOD, (3) DMH, (4) diphenhydramine (DPH), (5) 8-chlorotheophylline (8-Cl-T), and (6) theophylline (TEO). In this phase, we quantified glucose and insulin levels, behavior, physical activity, blood pressure, and vascular reactivity to phenylephrine and acetylcholine. Findings showed that DMH might improve a motor and physical stimulating effect but also increased NO levels in the lungs. DPH promoted a compulsive-like behavior that diminished with 8-Cl-T. Regarding cardiovascular effects, DMH decreased vascular reactivity to phenylephrine and acetylcholine. Finally, in the DMH formulation, 8-Cl-T was identified as the compound responsible for increasing blood pressure and heart rate.

Dietary supplements used by recreational and elite athletes for performance enhancement might contain undeclared, unlawfully added ingredients. One of those ingredients is 5α-hydroxy-laxogenin, which is sold in dietary supplements marketed as a natural compound with anabolic effects. It has been shown that 5α-hydroxy-laxogenin is not naturally occurring, but rather of synthetic origin. Previously, we observed that 5α-hydroxy-laxogenin can bind to and activate the androgen receptor in a cell-based bioassay. To investigate its androgenic potential in vivo, we treated orchiectomized rats with three different dosages of 5α-hydroxy-laxogenin for 2 weeks. Effects were neither observed on the wet weights of the androgen target tissues prostate, seminal vesicle or penis nor on the wet weights of the anabolic target tissue musculus levator ani or on skeletal hindlimb muscles. Au contraire, significantly higher atrophy was seen for some of the target tissues in the animals treated with the highest 5α-hydroxy-laxogenin dosage (36 mg/kg bw). While in silico docking supports the androgen receptor binding previously observed in vitro, we observed neither androgenic nor anabolic effects of 5α-hydroxy-laxogenin in vivo in castrated male rats.

An increasing number of novel Fc-fusion proteins and monoclonal antibodies (mAbs) are being developed as therapeutic agents for treating various diseases. Among these, there are inhibitors of the activin Type II receptor (ActRIIA and ActRIIB) signaling pathways and mAbs against nerve growth factor (NGF), which may be misused for performance enhancement in horseracing and equestrian sports. This study is aimed at developing a generic detection method for doping control analysis of nine targeted proteins, each containing the Fc domain of human IgG or IgG from other species in equine plasma, namely, three recombinant Fc-fusion proteins (sotatercept, follistatin-Fc (FST-Fc), and erythropoietin-Fc (EPO-Fc)) and six mAbs (bimagrumab, domagrozumab, garetosmab, landogrozumab, bedinvetmab (Librela), and frunevetmab (Solensia)). A generic workflow has been developed, involving affinity purification with commercially available Protein A magnetic beads followed by tryptic digestion and detection of 20 targeted peptides (with 2-3 diagnostic peptides for each targeted protein) using capillary flow high-performance liquid chromatography-high-resolution tandem mass spectrometry (HPLC-HRMS). The method identified all nine targeted proteins in spiked equine plasma with adequate sensitivity and precision, and for the first time, bedinvetmab (Librela) was detected and identified in plasma for at least 34 days after a single subcutaneous administration (0.5 mg/kg) to a Thoroughbred horse. The results have demonstrated the method's applicability to equine doping control. This generic method involving affinity purification by Protein A has provided a pragmatic and effective approach to cope with the doping control of novel Fc domain-containing proteins.

Carbon monoxide (CO) rebreathing is frequently used to determine hemoglobin mass (Hb_mass) during hypoxic or heat training and high-altitude research. Accurate and reliable carboxyhemoglobin (HbCO) determination is crucial for reliable Hb_mass measurements. The aim was therefore to explore the stability of HbCO and interchangeability of two Radiometer analyzers in the determination of Hb_mass. Twelve subjects performed a CO rebreathing test. Five capillary blood samples were taken before and after the CO rebreathing test and either analyzed immediately on site (three capillary tubes, Day 1, ABL 90) or stored at room temperature and sent to another laboratory for analysis 4-8 days later (two capillary tubes, ABL 825). Intraclass correlation coefficient (ICC) and relative typical error (TE) were calculated to compare both measurements. A paired sample t test was performed to detect potential differences between Day 1 (ABL 90) and Days 4-8 (ABL 825). A trivial mean difference was observed between the two measurements for ΔHbCO (0.05%, p = 0.01, d = -0.12) and Hb_mass (7.7 g, p = 0.01, d = 0.10). High reliability (ICC > 0.98) and low TE (< 0.91%) were found for ΔHbCO and Hb_mass. Immediate analysis with the same analyzer remains recommended despite trivial differences between measurements. However, when logistical issues (analyzer breakdown, extreme, and/or remote locations) do not allow optimal procedures, delayed analysis, potentially with a different analyzer, might be used as a viable alternative.

The physical advantages in elite power sports that allow men to surpass women are derived from the experience of male puberty. By creating testicular testosterone production 20-30-fold over women at any age, sustained exposure over years to adult male testosterone concentrations produces larger and stronger muscles, bones, and the cardiorespiratory system with a higher blood hemoglobin explaining those advantages. While genetic advantages in exercise performance unrelated to sex are accepted in elite sports, adults who have experienced male puberty but have female gender identity, such as male-to-female transgender or intersex (XY Disorders of Sexual Development, DSD), create a category-defeating conflict if they compete in female power sports. Transgender women seek feminization using estrogen treatment, which can suppress postpubertal endogenous testosterone but even sustained complete testosterone suppression leaves an unfair legacy of physical advantages. By contrast, XY DSDs do not seek hormonal feminization and recognize that testosterone suppression impedes their performance. Hence, understanding the biology of male-bodied athletes with female gender identity is crucial to effective management, which is geared toward maintaining fairness and safety for typical women competing in elite female events. Such sex-based restrictions are not required in recreational, junior, or nonprofessional sports or where physical advantages are not operative. After the IOC's controversial 2021 Framework document, a growing consensus among major international sports federations is establishing a working definition of male and female sports sex to facilitate fairness and safety in elite sports, which depend on power, strength, speed, or endurance.

Recent data indicate that the use of controlled substances is increasing in working life, which can negatively affect work environment, performance, and safety. Many employers have an alcohol and drug policy that describes routines for preventive measures and early detection of illicit drug use. This often includes drug tests that provide objective information about recent use, and can be done routinely, randomly, and on suspicion. For some substances, however, a positive drug test may also result from prescription as medicine. Controlled substances that are abused and prescribed include amphetamines (ADHD medication), benzodiazepines and opiates. In a 2023 study of 23,900 urine and oral fluid drug test results from Swedish workplaces, 4.6% tested positive for one or more controlled substances. Most samples were collected in connection with random testing (40%) and new employment (36%), whereas the highest proportions of drug-positive samples were observed in cases related to accidents or incidents, or on suspicion of drug use. The highest percentage of positive random drug tests was recorded in the construction sector. The most common substances were cannabis (> 40% of cases), amphetamine (> 20%), and cocaine and benzodiazepines (> 10% each). However, many samples containing opiates (71% of cases), amphetamine (63%) and benzodiazepines (44%) were verified by a specialist trained Medical Review Officer (MRO) to be due to medical prescription, while those containing cannabis or cocaine were almost entirely due to illicit drug use. Considering the potentially negative consequences of a positive drug test in working life, an MRO should verify the results before they become final.