LC-MS/MS Application in Pharmacotoxicological Field: Current State and New Applications.

Nowadays, it is vital to have new, complete, and rapid methods to screen and follow pharmacotoxicological and forensic cases. In this context, an important role is undoubtedly played by liquid chromatography-tandem mass spectrometry (LC-MS/MS) thanks to its advanced features. This instrument configuration can offer comprehensive and complete analysis and is a very potent analytical tool in the hands of analysts for the correct identification and quantification of analytes. The present review paper discusses the applications of LC-MS/MS in pharmacotoxicological cases because it is impossible to ignore the importance of this powerful instrument for the rapid development of pharmacological and forensic advanced research in recent years. On one hand, pharmacology is fundamental for drug monitoring and helping people to find the so-called "personal therapy" or "personalized therapy". On the other hand, toxicological and forensic LC-MS/MS represents the most critical instrument configuration applied to the screening and research of drugs and illicit drugs, giving critical support to law enforcement. Often the two areas are stackable, and for this reason, many methods include analytes attributable to both fields of application. In this manuscript, drugs and illicit drugs were divided in separate sections, with particular attention paid in the first section to therapeutic drug monitoring (TDM) and clinical approaches with a focus on central nervous system (CNS). The second section is focused on the methods developed in recent years for the determination of illicit drugs, often in combination with CNS drugs. All references considered herein cover the last 3 years, except for some specific and peculiar applications for which some more dated but still recent articles have been considered.

Forensic applications of hyperspectral imaging technique: a narrative review.

Hyperspectral imaging (HSI) collects and processes information from the entire electromagnetic spectrum to obtain the spectrum of each pixel in the image of a scene, with the aim of finding objects and identifying materials. It is a non-contact, non-destructive technology that can be used without modifying or altering the analysed target. Forensic analysis and crime scene investigations are two of the most investigated fields of application, being able to detect and analyse many types of evidence.In this paper we analysed the most commonly reported forensic science applications.The literature indicates that the fields in which HSI appears most promising are the analysis of blood traces, document forgery, gunshot residues and the identification of fingerprints.

Human Hepatocyte 4-Acetoxy-N,N-Diisopropyltryptamine Metabolite Profiling by Reversed-Phase Liquid Chromatography Coupled with High-Resolution Tandem Mass Spectrometry.

Tryptamine intoxications and fatalities are increasing, although these novel psychoactive substances (NPS) are not controlled in most countries. There are few data on the metabolic pathways and enzymes involved in tryptamine biotransformation. 4-acetoxy-N,N-diisopropyltryptamine (4-AcO-DiPT) is a synthetic tryptamine related to 4-hydroxy-N,N-diisopropyltryptamine (4-OH-DiPT), 4-acetyloxy-N,N-dipropyltryptamine (4-AcO-DPT), and 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT). The aim of this study was to determine the best 4-AcO-DiPT metabolites to identify 4-AcO-DiPT consumption through human hepatocyte metabolism and high-resolution mass spectrometry. 4-AcO-DiPT metabolites were predicted in silico with GLORYx freeware to assist in metabolite identification. 4-AcO-DiPT was incubated with 10-donor-pooled human hepatocytes and sample analysis was performed with reversed-phase liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-HRMS/MS) in positive- and negative-ion modes. Software-assisted LC-HRMS/MS raw data mining was performed. A total of 47 phase I and II metabolites were predicted, and six metabolites were identified after 3 h incubation following ester hydrolysis, O-glucuronidation, O-sulfation, N-oxidation, and N-dealkylation. All second-generation metabolites were derived from the only first-generation metabolite detected after ester hydrolysis (4-OH-DiPT). The metabolite with the second-most-intense signal was 4-OH-iPT-sulfate followed by 4-OH-DiPT-glucuronide, indicating that glucuronidation and sulfation are common in this tryptamine's metabolic pathway. 4-OH-DiPT, 4-OH-iPT, and 4-OH-DiPT-N-oxide are suggested as optimal biomarkers to identify 4-AcO-DiPT consumption.

An unusual case of suicidal double ligature strangulation.

As suicide by ligature strangulation is rare, the correct medico-legal diagnosis may be difficult to establish if there is no clear supporting circumstantial evidence. We report an unusual case of suicide by strangulation with a double ligature. Investigation of the scene of death and pathological findings at autopsy are reported and discussed. We emphasise the importance of an external examination and an on-the-spot investigation.

A particular case of accidental asphyxiation.

The case reported involved a 60-year-old man with psychiatric illness who was found dead at his home. He was almost naked and showed signs of death by violent asphyxiation, which led to the suspicion of homicide. Autopsy findings showed foreign material in the trachea and larynx. However, the partially digested content in his stomach, the study of the gastric content and the microscopic analysis of the airways made it possible to define this as accidental death due to inhalation of material from a diaper. Toxicological analysis detected the presence of phenytoin, valproic acid, and phenobarbital in his blood, with values within the therapeutic ranges. This is certainly a peculiar case, as particularly evident after careful review of the literature on deaths by asphyxiation in psychiatric patients. Furthermore, this study highlights the importance of a full autopsy and microscopic evaluation of any foreign bodies.

Clinical and psychosocial correlates of acute pain in herpes zoster.

BACKGROUND: Acute and persistent pain are the most significant clinical manifestations of herpes zoster (HZ), but the characteristics of acute pain in HZ patients have been inadequately investigated. OBJECTIVES: To correlate the severity of acute pain with clinical, demographic and psychosocial characteristics of HZ patients. STUDY DESIGN: Five hundred thirty-three patients with acute HZ were recruited by 119 dermatologists who collected medical and demographic data at diagnosis, provided counselling and therapy where appropriate and asked the patients to complete the Short Italian Questionnaire designed for comprehensive evaluation of HZ patients. RESULTS: In a univariate analysis, greater acute pain severity was significantly associated with female gender, number of dermatomes affected, presence of prodromal pain, abnormal sensations (dysesthesia), education level, anxiety and depression. Quality of life, even if greatly reduced, did not correlate with the intensity of pain. In a multivariate model, the intensity of pain was independently associated with the extent of rash (p=0.042), presence of prodromal pain (p=0.005), dysesthesia, education level (p=0.040), and depression (p<0.001), but not with gender, anxiety or quality of life. CONCLUSIONS: This study suggests that in patients with acute HZ the severity of the disease and depression at presentation are the main correlates of pain intensity.