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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]