Transdermal Nicotine Poisoning: A Rare Case Report of Occupational Exposure.

We report a case of accidental nicotine intoxication following transdermal exposure in a 22-year-old man with no medical history, who worked in a company manufacturing e-liquids for electronic cigarettes. He accidentally spilled 300 mL of pure nicotine solution (>99%) on his right leg without wearing protective clothing or a mask. Less than a minute later, he experienced dizziness, nausea, and headaches, followed by painful burning sensations in the affected area. He immediately removed his pants and washed his leg thoroughly with water. He presented to the emergency department two hours later, where he exhibited a respiratory rate of 25 cpm, a heart rate of 70 bpm, headaches, abdominal pain, pallor, and vomiting. He recovered without specific treatment five hours post-intoxication. Plasma levels of nicotine, cotinine, and hydroxycotinine were measured five hours after exposure using liquid chromatography-mass spectrometry. The concentrations found were 447 ng/mL for nicotine, 1254 ng/mL for cotinine, and 197 ng/mL for hydroxycotinine. Nicotine is an alkaloid that can be highly toxic, with doses of 30-60 mg being potentially fatal. Transdermal intoxication is rare, with very few cases reported in the literature. This case highlights the risk of acute intoxication through cutaneous exposure to nicotine-containing liquid products and the need for protective clothing when handling such products in a professional context.

Validation of a non-targeted method devoted to identification and quantitation of toxicologically relevant compounds in plasma with HRMS.

The objective of this study was to develop and validate a simple method using liquid chromatography hyphenated to high resolution mass spectrometry (HRMS) allowing both the performance of a non-targeted screening and the simultaneous quantification of 29 compounds of interest in clinical and forensic toxicology. Extraction was done with QuEChERS salts and acetonitrile, after addition of internal standard to 200 µL of human plasma samples. The mass spectrometer was an Orbitrap, with a heated electrospray ionization (HESI) probe. The analyses were carried out in full scan experiment with a nominal resolving power of 60,000 FWHM within the 125-650 m/z mass range, followed by four cycles of data dependent analysis (DDA) with a mass resolution of 16,000 FWHM. The untargeted screening was evaluated using 132 compounds, mean limit of identification (LOI) was 8.8 ng/mL (min = 0.05 ng/mL, max = 500 ng/mL) and mean limit of detection (LOD) was 0.25 ng/mL (min = 0.05 ng/mL, max = 5 ng/mL). The method was linear in the 5 to 500 ng/mL range (0.5 to 50 ng/mL for cannabinoids, 6-acetylmorphine and buprenorphine) with correlation coefficients > 0.99, intra- and inter-day accuracy and precision were < 15% for all compounds. The method was successfully applied to 31 routine samples.

Determination of cannabinoids content in light cannabis inflorescences sold in France.

In the last 2 years, the number of shops selling CBD-rich THC-deprived cannabis flowers (CrTd) has increased considerably in France as in many European countries. The objective of this study was to determine the actual composition of the samples sold in these stores and to discuss regulatory consequences that may affect users. Samples were provided from shops in the region Provence-Alpes Cote d'Azur (PACA), France. Pictures of the samples were taken before they were weighed then crushed. Twenty milligrams were diluted in 10 ml heptane ethyl acetate (7:1; v:v) for analysis by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The method was validated according to SWGTOX guidelines for the quantification of cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC) and cannabinol (CBN). Thirty-nine samples obtained between November 2021 and January 2022 in the PACA region were analyzed in this study. Mean content was 0.32% (0.03%-0.77%; STDV = 0.17%; n = 39) for THC, 2.23% (0.01%-5.97%; STDV = 1.29%; n = 39) for CBD and 0.01% (0.004%-0.025%; STDV = 0.01%; n = 19) for CBN. THC content over the threshold defined by the European legislation (>0.3%) was found in 18 of the 39 samples analyzed together with a CBD content <1% in nine samples (23%). None of the products analyzed had health risk messages on the packaging. The consumption of these products may lead to the presence of THC in biological fluids, which can be detected by screening. Users may then find themselves in breach of the law particularly when driving. Consumers should therefore be informed both about the actual composition of these products and about the legal and health risks they run.

Determination of Prenatal Substance Exposure Using Meconium and Orbitrap Mass Spectrometry.

The aim of this study was to develop and to validate a toxicological untargeted screening relying on LC-HRMS in meconium including the detection of the four main classes of drugs of abuse (DoA; amphetamines, cannabinoids, opioids and cocaine). The method was then applied to 29 real samples. Analyses were performed with a liquid chromatography system coupled to a benchtop Orbitrap operating in a data-dependent analysis. The sample amount was 300 mg of meconium extracted twice by solid phase extraction following two distinct procedures. Raw data were processed using the Compound Discoverer 3.2 software (Thermo). The method was evaluated and validated on 15 compounds (6-MAM, morphine, buprenorphine, norbuprenorphine, methadone, EDDP, amphetamine, MDA, MDMA, methamphetamine, cocaine, benzoylecgonine, THC, 11-OH-THC, THC-COOH). Limits of detection were between 0.5 and 5 pg/mg and limits of identification between 5 and 50 pg/mg. Mean matrix effect was between -79 and -19% (n = 6) and mean overall recovery between 18 and 73% (n = 6) at 100 pg/mg. The application allows the detection of 88 substances, including 47 pharmaceuticals and 15 pharmaceutical metabolites, cocaine and its metabolites, THC and its metabolites, and natural (morphine, codeine) and synthetic (methadone, buprenorphine, tramadol, norfentanyl) opioids. This method is now used routinely for toxicological screening in high-risk pregnancies.