Toxicological analysis of a "poison vial" found in the remains of an SS soldier (Maltot, Normandy, France).

In Maltot (Normandy, France), one grave containing the remains of a German soldier, who died in 1944, was excavated amongst other graves and isolated elements. A dozen whole vials were unearthed, resulting in questions about their content. Various screenings were carried out on the contents of one single vial: HPLC-DAD and HR-LC-MS screening after 1/10 dilution in mobile phase, GC-MS and HS-GC-MS after 1/10 dilution in methanol, multi-element research by HR-ICP-MS after total mineralization, and cyanide analysis. Analyzed vial contained approximately 300 µL of a colorless, water-immiscible liquid with a characteristic solvent odor. HPLC-DAD, GC-MS, HR-LC-MS/MS, ICP-MS, and cyanide screenings were negative excluding the presence of cyanide, arsenic, barbiturates, amphetamines, or narcotics. HS-GC-MS analysis highlighted the presence of ethanol, chloroform, and diethyl ether at significant concentrations. Chloroform and diethyl ether were anesthetic products mainly reserved for urgent situations. We hypothesized that the soldier may have been a combat medic working on battlefields. as he was wounded, another possibility could be that he may have used the vials to relieve his pain; however, the immediate severity of the wounds drove us to assess the second hypothesis of delayed death as being less plausible. The high number of vials containing ethanol, chloroform, and diethyl ether, and the massive blood loss leading to quick death led us to support the combat medic or paramedic hypothesis.

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). The aim of this study was to present the qualitative and quantitative results of toxicological analyses of pharmaceutical and dietary supplements seized from the black market among bodybuilders in France. All dietary supplements and pharmaceuticals seized from the black market and addressed to the laboratory for a qualitative and quantitative analysis between January 2016 and December 2019 were included in the study. A screening was carried out by gas chromatography-mass spectrometry and liquid chromatography-high resolution mass spectrometry. Identified compounds were quantified by liquid chromatography-tandem mass spectrometry. One hundred and ten products were seized and submitted to the laboratory for identification of active compounds and quantification: 75 pharmaceuticals and 35 dietary supplements. This included 39 oily and 3 aqueous solutions for intramuscular injection, 34 tablets, 13 capsules, 14 powders, 4 liquids and 3 lyophilizates. Among the pharmaceuticals, 25/75 (33%) were substandard (dosage not on the acceptable range defined for original products), 24/75 (32%) were counterfeit (qualitative formulation does not match the label) and 14/75 (19%) were original (qualitative formulation and levels of active ingredients fully matches the declared formulation. The analysis of the 12 remaining products revealed a correct qualitative content for 11/75 (15%), but quantitation could not be carried out because of the lack of reference standards at the time of the analysis. Fifty-four pharmaceuticals contained anabolic-androgenic steroids (AAS). Four out of 54 (7.4%) AAS were found as original, 8/54 (15%) could not be quantified (one with wrong active ingredient), corresponding to 43/54 (80%) AAS being non-original. In contrast, only 1/35 dietary supplement (3%) was adulterated, with a doping substance (1,3-dimethylbutylamine, DMBA). This work allows to show that France is not spared by the trafficking of PIEDs. The use of counterfeit drugs in mainstream population is an underestimated public health issue.

Development and validation of a liquid chromatography-tandem mass spectrometry method for simultaneous detection of 10 illicit drugs in oral fluid collected with FLOQSwabs™ and application to real samples.

According to French law, the roadside testing for drugs of abuse (DOA) should be performed in oral fluid (OF) using an immunological screening kit. If the screening is positive, confirmation has to be done in OF collected by a special swab, called the FLOQSwab™ (FS). Unlike other sampling kits, this device was not designed to collect OF since it does not contain an elution buffer. An analytical method was developed for the simultaneous detection of 10 DOA under control in France: tetrahydrocannabinol (THC) at 1 ng/mL, and cocaine, benzoylecgonine (BZE), morphine, 6-monoacetylmorphine (6-MAM), amphetamine, methamphetamine, 3,4-methylenedioxy-N-ethylamphetamine (MDEA), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxy-N-methylamphetamine (MDMA) at 10 ng/mL. Samples were eluted using the Quantisal® buffer and extracted by liquid-liquid extraction for THC and by solid-phase extraction for the remaining analytes. Analyses were performed by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The validated method made it possible to detect the concentrations required by law and was successfully applied to samples from drivers who screened positive. The main limitations of this kit are the large variability of the collected OF volume and the poor stability of DOA in OF, requiring the use of a conservation buffer.

A LC/MS/MS micro-method for human plasma quantification of vemurafenib. Application to treated melanoma patients.

As previously shown for imatinib, therapeutic drug monitoring (TDM) of vemurafenib should be important to measure efficacy of the treatment in melanoma patient. A micro-method based on liquid chromatography coupled to triple quadrupole spectrometry detection using only 10µL of plasma was validated. A simple protein precipitation with water/acetonitrile was used after addition of vemurafenib-(13)C6 as internal standard. The ion transitions used to monitor analytes were m/z 490.2→m/z 255.2 and m/z 383.3 for vemurafenib and m/z 496.2→m/z 261.2 and m/z 389.3 for vemurafenib-(13)C6. Calibration curves were linear in the 0.1-100µg/mL range, the limits of detection and quantification being 0.01µg/mL and 0.1µg/mL, respectively. The intra- and inter-assay precisions evaluated at 0.1, 0.3, 15, 45 and 80µg/mL were lower than 13.3% and the accuracies were in the 93.7-105.8 range. No matrix effect was observed. At steady state, the results of TDM of vemurafenib in 26 patients treated by 960mg twice daily (n=60 samples), 13 patients with 740mg twice daily (n=13) and one with 1200mg twice daily (n=3) showed a great variability of the pharmacokinetics of this compound.