Introduction: The analysis of novel psychoactive substances (NPS) represents a challenge in forensic toxicology, due to the high number of compounds characterized by different structures and physicochemical properties both among different subclasses and within a single subclass of NPS. The aim of the present work is the development and validation of a targeted liquid chromatography tandem mass spectrometry (LC‐MS/MS) method for the detection of NPS in whole blood.Materials and methods: A protein‐precipitation based LC‐MS/MS method for the detection of more than 180 NPS was developed and validated by assessing the following parameters: selectivity, linearity, accuracy, precision, limit of detection (LOD) and of quantification (LOQ) recovery, and matrix effect. Then, the method was applied to real forensic samples.Results: The method allowed the identification of 132 synthetic cannabinoids, 22 synthetic opioids, and 28 substances among synthetic cathinones, stimulants, and other drugs. Validation was successfully achieved for most of the compounds. Linearity was in the range of 0.25–10 ng/ml for synthetic cannabinoids and 0.25–25 ng/ml for other drugs. Accuracy and precision were acceptable according to international guidelines. Three cases tested positive for fentanyl and ketamine, in the setting of emergency room administration.Conclusions: The present methodology represents a fast, not expensive, wide‐panel method for the analysis of more than 180 NPS by LC‐MS/MS, which can be profitably applied both in a clinical context and in postmortem toxicology.
Purpose: Cumyl-PEGACLONE was the first synthetic cannabinoid (SC) with a γ-carbolinone core structure detected in forensic casework and, since then, it has dominated the German SC-market. Here the first four cases of death involving its fluorinated analog, 5F-Cumyl-PEGACLONE, a recently emerged γ-carbolinone derived SC, are reported.Methods: Complete postmortem examinations were performed. Postmortem samples were screened by immunoassay, gas chromatography mass spectrometry (GC–MS) or liquid chromatography tandem mass spectrometry. For quantification of SCs, the standard addition method was employed. Herbal blends were analyzed by GC–MS. In each case of death, the Toxicological Significance Score (TSS) was assigned to the compound.Results: 5F-Cumyl-PEGACLONE was identified at concentrations ranging 0.09–0.45 ng/mL in postmortem femoral blood. In case 1, signs of hypothermia and kidney bleedings were noted. Despite a possible tolerance due to long term SC use, a TSS of 3 was assigned. In case 2, an acute heroin intoxication occurred and a contributory role (TSS = 1) of 5F-Cumyl-PEGACLONE was suggested. In case 3, a prisoner was found dead. GC–MS analysis of herbal blends, retrieved in his cell together with paraphernalia, confirmed the presence of 5F-Cumyl-PEGACLONE and a causative role was deemed probable (TSS = 2). In case 4, the aspiration of gastric content due to a SC-induced coma was observed (TSS = 3).Conclusions: 5F-Cumyl-PEGACLONE is an emerging and extremely potent SC which raises serious public health concerns. A comprehensive analysis of circumstantial, clinical, and postmortem findings, as well as an in-depth toxicological analysis is necessary for a valid interpretation and for the assessment of the toxicological significance.
In the past years, new psychoactive substances (NPS) started circulating in prisons, leading to health risks and challenges for the criminal justice system. Seizures of papers and cards impregnated with synthetic cannabinoid (SCs) have been reported. In November 2021, a letter suspected to be drug‐infused was sent from a German prison to this laboratory. Toxicological analyses were performed by means of gas chromatography–mass spectrometry (GC–MS) for drug screening and liquid chromatography–tandem mass spectrometry (LC–MS/MS) as well as high‐performance (HP) LC with diode‐array detection (DAD) for semi‐quantification of the compounds. The novel synthetic opioid (NSO) AP‐237 was detected on the letter, with an estimated concentration of 1.2 μg/cm2, together with the SCs MDMB‐4en‐PINACA (77 μg/cm2) and 5F‐ADB (6.5 μg/cm2). To the best of the authors' knowledge, this is the first time an NSO was detected on a drug‐infused paper seized in a prison. Highly potent NSOs could easily be dissolved in organic solvents to produce impregnated papers and textiles, and this might represent a serious threat to the health of people in prison. Given the inhomogeneity in drug concentrations, health risks might in particular arise from the consumption of highly concentrated areas of the paper—so‐called “hot spots”—especially when highly potent NSOs are used for infusion. Laboratories engaged in analyzing such impregnated papers should be aware of the potential presence of NSOs and adapt the respective methods accordingly.
Fetal inflammatory response syndrome (FIRS) represents the fetal inflammatory reaction to intrauterine infection or injury, potentially leading to multiorgan impairment, neonatal mortality, and morbidity. Infections induce FIRS after chorioamnionitis (CA), defined as acute maternal inflammatory response to amniotic fluid infection, acute funisitis and chorionic vasculitis. FIRS involves many molecules, i.e., cytokines and/or chemokines, able to directly or indirectly damage fetal organs. Therefore, due to FIRS being a condition with a complex etiopathogenesis and multiple organ dysfunction, especially brain injury, medical liability is frequently claimed. In medical malpractice, reconstruction of the pathological pathways is paramount. However, in cases of FIRS, ideal medical conduct is hard to delineate, due to uncertainty in diagnosis, treatment, and prognosis of this highly complex condition. This narrative review revises the current knowledge of FIRS caused by infections, maternal and neonatal diagnosis and treatments, the main consequences of the disease and their prognoses, and discusses the medico-legal implications.