Pascal Houzé

Drug facilitating sexual assault (DFSA) corresponds to sexual activity occurring whereas the victim is unable to express consent due to the action of drug. Although use of sedative and amnesic drug in DFSA such as benzodiazepines and gamma-hydroxybutyrate (GHB) is widely described in the medical literature, there is a lack of information regarding the involvement of amphetamine derivatives in this context, particularly synthetic cathinones. Herein, we report a case of a 19-year-old woman who presents herself into the emergency department following an acute alcoholic intoxication and a suspected DFSA after going in a nightclub. The emergency toxicological screening on the plasma and urine of the patient, performed through liquid chromatography coupled to high resolution tandem mass spectrometry (LC-HRMS) on target and non-target mode and with gas chromatography coupled to high resolution mass spectrometry (GC-HRMS) enabled the detection of 4-bromomethcathinone (4-BMC), a new psychoactive substance (NPS) of the cathinone family. The demethylated and reduced metabolites of the drug were also found in both plasma and urine. No other substance was identified except ethanol which was quantified in gas chromatography–flame ionization detection (GC-FID) and diazepam with its metabolites, this last one having been administrated in the emergency department. As far as we know, this report described the first case of DFSA involving this halogenated derivative of cathinone and consequently, highlights the need for toxicologists to systematically investigate with specific analytical methods the potential presence of NPS in case of DFSA.

We report a case of systemic organophosphate (OP) poisoning in a young child following the use of a household shampoo containing diazinon. In previous reported cases, diagnosis is typically made rapidly and indirectly through decreased cholinesterase activity and identification of OPs in commercial containers. In our case, however, the diagnosis was significantly delayed due to nonspecific clinical signs and a language barrier between the family and medical staff, resulting in the development of an intermediate syndrome. Initial symptoms included gastrointestinal disturbances, followed several hours later by neurological and respiratory complications. Plasma, urinary, and hair arsenic levels were first investigated due to the use of a product which may contain organometallic copper acetoarsenite complex. All arsenic concentrations were within physiological concentrations. Clinical presentation and biological cholinesterase activity (313 U/L vs. reference 1900–3800 U/L) later supported the diagnosis of OP poisoning. This hypothesis was reinforced by the analysis of the household shampoo indicating the presence of diazinon. Furthermore, despite the delayed diagnosis, non-targeted high-resolution mass spectrometry (LC-HR-MS/MS) identified diazinon in plasma and multiple phase I metabolites, including the specific marker IMPY, in both plasma and urine. Four previously undescribed metabolites and one phase II metabolite, hydroxy-IMPY-glucuronide, were also detected. Pralidoxime methylsulfate (Contrathion™) was administered on day 4, following toxicological confirmation and lack of clinical improvement. Although late, this treatment led to gradual neurological recovery, suggesting possible slow “aging” of diazinon-inhibited acetylcholinesterase. Nonetheless, the child developed persistent sequelae including hypotonia, peripheral neuropathies, and respiratory dysfunction consistent with intermediate syndrome. This case highlights the importance of considering OP poisoning even in atypical presentations and illustrates the utility of non-targeted HRMS screening in providing direct evidence of exposure when conventional approaches are inconclusive.

Nitazenes represent an emerging class of new synthetic opioids characterized by a high-potency μ-opioid receptor (MOR) agonist activity. Background: We report two 20-year-old males who presented with severe neurorespiratory depression with typical opioid syndrome, but no opioid identification based on routine blood and urine screening tests. The first patient recovered with supportive care, mechanical ventilation, and naloxone infusion, whereas the second patient developed post-anoxic cardiac arrest and died from brain death. Methods: A complementary comprehensive toxicological screening using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) was performed, and data were processed using a dedicated molecular network strategy to profile the metabolites. Results: Protonitazene and protonitazepyne, two nitazenes differing in their ethylamine moieties (i.e., a diethyl versus a pyrrolidine substitution, respectively), were identified. We found an extensive metabolism of protonitazene, leading to the identification of multiple phase I (resulting from hydroxylation, N-desethylation, and O-despropylation) and phase II (resulting from glucuronidation) metabolites. By contrast, protonitazepyne metabolism appeared limited, with one metabolite annotated confidently, protonitazepyne acid, which resulted from the oxidative pyrrolidine ring cleavage. Concusions: To conclude, nitazene detection is highly challenging due to its extensive structural and metabolic diversity. Our findings highlight the contribution of the untargeted LC-HRMS screening approach and suggest that diagnostic product ions can serve as robust markers for nitazene identification.

Plant-based food supplements (FS) of doubtful traceability have now emerged as a new threat to human health. Food supplements adulterated with pharmaceutical ingredients are considered “medicines in disguise” by regulatory authorities, which is a sub-category of falsified medicines. In the context of illegal manufacture and trade, as well as in the absence of an official phyto- and/or pharmacovigilance system, emergency departments and poison control centers constitute a early warning system for detecting ingested suspect FS. In the present investigation, we set up efficient workflows for the systematic characterization of adulterated plant-based FS in the context of an original local early warning alert system (i.e., FalsiMedTrack) involving an emergency department, a poison center, and academic analytical chemistry laboratories. Fit-for-purpose cross-analytical methods were employed, including sophisticated methods such as liquid chromatography coupled to high-resolution mass spectrometry, nuclear magnetic resonance, X-ray powder diffraction, as well as the most accessible and affordable HPLC method with UV/DAD detection. The strategy was applied successfully to typical cases of suspect plant-based health products, i.e., sample incriminated in patients experiencing side effects and herbal products currently commercialized for their “amazing health benefits”. The samples contained active pharmaceutical ingredients, including diclofenac, piroxicam, dexamethasone 21-acetate, and sibutramine. We provided evidence of “medicines in disguise” presented as food supplements, which raises concerns about their quality and safety.

In toxicology, screenings are routinely performed using chromatographic methods coupled to detection systems such as high-resolution mass spectrometry (HR/MS). The increase in specificity and sensitivity of HRMS is responsible for the development of methods for alternative samples such as Volumetric Adsorptive Micro-Sampling. Whole blood overloaded with 90 drugs was sampled with 20 µL Mitra^TM to optimize the pre-analytical step as well as to determine the identification limits of drugs. Elution of chemicals was carried out in a solvent mixture through agitation and sonication. After dissolution, 10 μL was injected into the chromatographic system coupled to the Orbitrap^TM HR/MS. Compounds were confirmed against the laboratory library. The clinical feasibility was assessed in fifteen poisoned patients using the simultaneous sampling of plasma, whole blood and Mitra^TM. The optimized extraction procedure allowed us to confirm 87 compounds out of the 90 present in the spiked whole blood. Cannabis derivatives were not detected. For 82.2% of the investigated drugs, the identification limits were below 12.5 ng·mL⁻¹, with the extraction yields ranging from 80.6 to 108.7%. Regarding the patients’ analysis, 98% of the compounds in plasma were detected in Mitra^TM compared to whole blood, with a satisfying concordance (R² = 0.827). Our novel screening approach opens new insights into different toxicologic fields appropriate for pediatrics, forensics or to perform mass screening.

Background. Sequestration of vancomycin in ST^® filters used in continuous renal therapy is a pending question. Direct vancomycin-ST^® interaction was assessed using the in vitro NeckEpur^® technology. Method. ST150^® filter and Prismaflex dialyzer, Baxter-Gambro, were used. Two modes were assessed in duplicate: (i) continuous diafiltration (CDF): 4 L/h, (ii) continuous dialysis (CD): 2.5 L/h post-filtration. Results. The mean initial vancomycin concentration in the central compartment (CC) was 51.4 +/− 5.0 mg/L. The mean percentage eliminated from the CC over 6 h was 91 +/− 4%. The mean clearances from the CC by CDF and CD were 2.8 and 1.9 L/h, respectively. The mean clearances assessed using cumulative effluents were 4.4 and 2.2 L/h, respectively. The mean percentages of the initial dose eliminated in the effluents from the CC by CDF and CD were 114 and 108% with no detectable sequestration of vancomycin in both modes of elimination. Discussion. Significant sequestration adds a clearance to that provided by CDF and CD. The study provides multiple evidence from the CC, the filter, and the effluents of the lack of an increase in total clearance in comparison with the flow rates without significant sequestration in the ST^® filter comparing cumulative effluents to the initial dose in the CC. Conclusions. There is no evidence ST^® filters directly sequestrate vancomycin.