Body fluid contamination in the context of an adverse analytical finding in doping: About a case involving ostarine.

Ostarine, also known as MK-2866 or enobosarm, is a selective androgen receptor modulator (SARM). It has anabolic properties and as such is widely used in doping, accounting in 2021 for 25 % of the adverse analytical findings (AAF) among the class S1.2 "Other anabolic agents" of products banned by the World Anti-Doping Agency, to which it belongs.

Can inhaled cannabis users accurately evaluate impaired driving ability? A randomized controlled trial.

Aims: To study the effect of inhaled cannabis on self-assessed predicted driving ability and its relation to reaction times and driving ability on a driving simulator.

Participants And Methods: 30 healthy male volunteers aged 18-34: 15 chronic (1-2 joints /day) and 15 occasional (1-2 joints/week) consumers. Self-assessed driving confidence (visual analog scale), vigilance (Karolinska), reaction time (mean reciprocal reaction time mRRT, psychomotor vigilance test), driving ability (standard deviation of lane position SDLP on a York driving simulator) and blood concentrations of delta-9-tétrahydrocannabinol (THC) were measured before and repeatedly after controlled inhalation of placebo, 10 mg or 30 mg of THC mixed with tobacco in a cigarette.

Proton-Pump Inhibitors and Serum Concentrations of Uremic Toxins in Patients with Chronic Kidney Disease.

Use of proton-pump inhibitors (PPIs) is common in patients with chronic kidney disease (CKD). PPIs and many uremic toxins (UTs) are eliminated by the kidney's tubular organic anion transporter system. In a cross-sectional study, we sought to evaluate the association between PPI prescription and serum concentrations of various UTs.

Correlation between Saliva Levels and Serum Levels of Free Uremic Toxins in Healthy Volunteers.

The objective of the present study was to investigate the putative correlation between the saliva concentration and free serum concentration for 10 uremic toxins (UTs; eight protein-bound solutes: 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), hippuric acid (HA), indole-3-acetic acid (3-IAA), indoxyl sulfate (I3S), kynurenic acid (KA), kynurenine (KYN), p-cresyl glucuronide (pCG), and p-cresyl sulfate (pCS); two free, water-soluble, low-molecular weight solutes: phenylacetylglutamine (PAGN) and trimethylamine N-oxide (TMAO); and three precursors: tyrosine (Tyr), phenylalanine, and tryptophan). Saliva samples and blood samples were collected simultaneously from 18 healthy volunteers. After the addition of internal standards, 50 µL of saliva or serum were precipitated with methanol.

Indoxyl sulfate impairs erythropoiesis at BFU-E stage in chronic kidney disease.

Chronic kidney disease (CKD) is a global health condition characterized by a progressive deterioration of kidney function. It is associated with high serum levels of uremic toxins (UT), such as Indoxyl Sulfate (IS), which may participate in the genesis of several uremic complications. Anemia is one of the major complications in CKD patients that contribute to cardiovascular disease, increase morbi-mortality, and is associated with a deterioration of kidney failure in these patients.

The association between TMAO, CMPF, and clinical outcomes in advanced chronic kidney disease: results from the European QUALity (EQUAL) Study.

Background: Trimethylamine N-oxide (TMAO), a metabolite from red meat and fish consumption, plays a role in promoting cardiovascular events. However, data regarding TMAO and its impact on clinical outcomes are inconclusive, possibly due to its undetermined dietary source.

Objectives: We hypothesized that circulating TMAO derived from fish intake might cause less harm compared with red meat sources by examining the concomitant level of 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), a known biomarker of fish intake, and investigated the association between TMAO, CMPF, and outcomes.

Validation of a liquid chromatography coupled to tandem mass spectrometry method for simultaneous quantification of tryptophan and 10 key metabolites of the kynurenine pathway in plasma and urine: Application to a cohort of acute kidney injury patients.

A sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of tryptophan (Trp) and ten metabolites of kynurenine pathway, including kynurenine (Kyn), 3-hydroxy-kynurenine (3-HK), kynurenic acid (KA), xanthurenic acid (XA), 3-Hydroxy-anthranilic acid (3-HANA), quinolinic acid (QA), nicotinic acid mononucleotide (NaMN), picolinic acid (Pic), nicotinamide (NAM) and nicotinic acid (NA) in both plasma and urine. This LC-MS/MS method was used to predict the occurrence of acute kidney injury (AKI) in a cohort of patients with cardiac surgery under cardiopulmonary bypass (CPB). Urinary concentrations of Pic, as well as Pic to Trp and Pic to 3-HANA ratios were highly predictive of an AKI episode the week after CPB, indicating that Pic could be a predictive biomarker of AKI.

Glyphosate and aminomethylphosphonic acid in human hair quantified by an LC-MS/MS method.

An LC-MS/MS method for hair testing of glyphosate and aminomethylphosphonic acid (AMPA), its main biodegradation product, has been developed. After decontamination, 50 mg of hair was ground and sonicated in water for 2 h. The method was fully validated in the 5-500 pg/mg range for glyphosate and 10-500 pg/mg for AMPA, and the limits of detection were 2 and 5 pg/mg, respectively.

The relationship between uremic toxins and symptoms in older men and women with advanced chronic kidney disease.

Background: Patients with stage 4/5 chronic kidney disease (CKD) suffer from various symptoms. The retention of uremic solutes is thought to be associated with those symptoms. However, there are relatively few rigorous studies on the potential links between uremic toxins and symptoms in patients with CKD.

Loss of Consciousness and Visual Hallucinations Related to 5-MeO-DALT Intake, a Case Report Confirmed by Toxicological Analyses.

5-MeO-DALT or 5-methoxy-N,N-diallyltryptamine is a derivative of tryptamines, consumed for its hallucinogenic and entheogenic effects. We report the case of a 46-year-old-man, presenting with a brief loss of consciousness and visual hallucinations, after the consumption of three 5-MeO-DALT tablets bought online. Liquid chromatography coupled to tandem mass spectrometry method was performed, and 5-MeO-DALT was quantified in both the tablets (32.

Population Pharmacokinetics of Hydroxychloroquine and 3 Metabolites in COVID-19 Patients and Pharmacokinetic/Pharmacodynamic Application.

We develop a population pharmacokinetic model for hydroxychloroquine (HCQ) and three of its metabolites (desethylhydroxychloroquine, Des HCQ; desethylchloroquine, DesCQ; and didesethylchloroquine, didesCQ) in COVID-19 patients in order to determine whether a pharmacokinetic (PK)/pharmacodynamic (PD) relationship was present. The population PK of HCQ was described using non-linear mixed effects modelling. The duration of hospitalization, the number of deaths, and poor clinical outcomes (death, transfer to ICU, or hospitalization ≥ 10 d) were evaluated as PD parameters.

Poppers, by Inducing HHV-8 Virion Production, Can Act as a Promoter for HHV-8 Transmission in Men Who Have Sex With Men.

Environmental factors were reported to increase the risk of human herpesvirus 8 (HHV-8) transmission. In a population of men who have sex with men (MSM), we found evidence that chemsex was associated with human herpesvirus 8 seropositivity in vivo and that poppers induced HHV-8 virion production in vitro. Our finding may explain the higher HHV-8 transmission in MSM.

Analysis of pharmaceutical products and dietary supplements seized from the black market among bodybuilders.

Substandard/counterfeit drugs are a growing global problem. According to the World Health Organisation, counterfeit medicines are medicines that are mislabelled deliberately and fraudulently regarding their identity and/or source. In high income countries, drugs seized are mainly represented by performance and image enhancing drugs (PIEDs).

Metabolic profiling of deschloro-N-ethyl-ketamine and identification of new target metabolites in urine and hair using human liver microsomes and high-resolution accurate mass spectrometry.

The aim of this study was to identify new markers of deschloro-N-ethyl-ketamine (O-PCE), a ketamine analogue that has been involved in acute intoxications with severe outcomes including death and whose metabolism has never been studied before. In vitro study after 2-h incubation with pooled human liver microsomes (HLMs) cross-checked by the analysis of urine and hair from a 43-year-old O-PCE user (male) were performed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Acquired data were processed by the Compound Discoverer® software, and a full metabolic profile of O-PCE was proposed.

Atropine-induced toxicity after off-label sublingual administration of eyedrop for sialorrhoea treatment in neurological disabled patients.

Sialorrhea is a troublesome and disabling symptom defined by the unintentional loss of saliva from the mouth, usually associated with swallowing disorders. Today there is no consensus about the management of sialorrhoea, but off-label use of ophthalmic atropine eyedrop administered sublingually may offer benefits, despite limited safety data. We report 2 cases of atropine overdose after sublingual administration illustrating that atropine can expose to severe adverse effects when administered sublingually.

Evaluation of Drug Abuse by Hair Analysis and Self-Reported Use Among MSM Under PrEP: Results From a French Substudy of the ANRS-IPERGAY Trial.

Background: We used the Agence nationale de Recherches sur le sida et les hépatites virales (ANRS)-IPERGAY trial to qualitatively and quantitatively measure drug use among men who have sex with men under preexposure prophylaxis using 2 different methods, to better understand and collectively respond to risky practices.

Method: We included 69 volunteers of the ANRS-IPERGAY trial. We measured drug use by 2 methods: (1) drug detection by hair analysis and (2) reported drug use by self-reported drug consumption.

Molecular adsorbent recirculating system (MARS) and continuous veno-venous hemodiafiltration (CVVHDF) for diltiazem removal: An in vitro study.

The objective of the present study was to evaluate the efficacy of the molecular adsorbent recirculating system (MARS) vs continuous veno-venous hemodiafiltration (CVVHDF). Diltiazem poisoning was simulated in a central compartment consisting in a 5L dialysis solute spiked with diltiazem at two different toxic concentrations: 750 and 5000 µg/L. For CVVHDF, mean extraction coefficients (EC = (in concentration - out concentration)/in concentration) were concentration-dependent with a decrease all along the dialysis.

Population pharmacokinetics of lopinavir/ritonavir in Covid-19 patients.

Objective: To develop a population pharmacokinetic model for lopinavir boosted by ritonavir in coronavirus disease 2019 (Covid-19) patients.

Methods: Concentrations of lopinavir/ritonavir were assayed by an accredited LC-MS/MS method. The population pharmacokinetics of lopinavir was described using non-linear mixed-effects modeling (NONMEM version 7.

Quantification of plasma remdesivir and its metabolite GS-441524 using liquid chromatography coupled to tandem mass spectrometry. Application to a Covid-19 treated patient.

Objectives: A method based on liquid chromatography coupled to triple quadrupole mass spectrometry detection using 50 µL of plasma was developed and fully validated for quantification of remdesivir and its active metabolites GS-441524.

Methods: A simple protein precipitation was carried out using 75 µL of methanol containing the internal standard (IS) remdesivir-13C6 and 5 µL ZnSO4 1 M. After separation on Kinetex® 2.

Development and validation of liquid chromatography-tandem mass spectrometry targeted screening of 16 fentanyl analogs and U-47700 in hair: Application to 137 authentic samples.

This study was to validate a LC-MS/MS method for the determination of 17 new synthetic opioids (NSOs) in hair including 3-fluorofentanyl, 3-methylfentanyl, acetylfentanyl, acetylnorfentanyl, alfentanyl, butyrylfentanyl, butyrylnorfentanyl, carfentanil, fentanyl, furanylfentanyl, furanylnorfentanyl, methoxyacetylfentanyl, norcarfentanil, norfentanyl, ocfentanil, sufentanil, and U-47700, and to apply it to 137 authentic samples. Twenty milligrams of hair was decontaminated in dichloromethane and underwent liquid extraction. 10 μL of the reconstituted residue were injected onto the system.