Publications by authors named "Annagiulia Di Trana"

17 Publications

  • Page 1 of 1

Editorial: Psychiatric and Pharmacotoxicological Insights on Appearance and Performance Enhancing Drugs.

Front Psychiatry 2022 26;13:918482. Epub 2022 May 26.

Section of Legal Medicine, Department of Excellence of Biomedical Sciences and Public Health, Polytechnic University of Marche, Ancona, Italy.

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http://dx.doi.org/10.3389/fpsyt.2022.918482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178271PMC
May 2022

Liquid Chromatography High Resolution Mass Spectrometry in Forensic Toxicology: What Are the Specifics of Method Development, Validation and Quality Assurance for Comprehensive Screening Approaches?

Curr Pharm Des 2022 May 26. Epub 2022 May 26.

Institute of Forensic Medicine, Jena University Hospital, Jena, Germany.

The use of High Resolution Mass Spectrometry (HRMS) has increased over the past decade in clinical and forensic toxicology, especially for comprehensive screening approaches. Despite this, few guidelines of this field have specifically addressed HRMS issues concerning compound identification, validation, measurement uncertainty and quality assurance. To fully implement this technique, certainly in an era in which the quality demands for laboratories are ever increasing due to various norms (e.g. the International Organization for Standardization's ISO 17025), these specific issues need to be addressed. This manuscript reviews 26 HRMS-based methods for qualitative systematic toxicological analysis (STA) published between 2011 and 2021. Key analytical data such as samples matrices, analytical platforms, numbers of analytes and employed mass spectral reference databases/libraries as well as the studied validation parameters are summarized and discussed. The article further includes a critical review of targeted and untargeted data acquisition approaches, available HRMS reference databases and libraries as well as current guidelines for HRMS data interpretation with a particular focus on identification criteria. Moreover, it provides an overview on current recommendations for the validation and determination measurement uncertainty of qualitative methods. Finally, the article aims to put forward suggestions for method development, compound identification, validation experiments to be performed, and adequate determination of measurement uncertainty for this type of wide-range qualitative HRMS-based methods.
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http://dx.doi.org/10.2174/1381612828666220526152259DOI Listing
May 2022

Synthetic Benzimidazole Opioids: The Emerging Health Challenge for European Drug Users.

Front Psychiatry 2022 25;13:858234. Epub 2022 Mar 25.

Unit of Forensic Toxicology, Section of Legal Medicine, Department of Excellence of Biomedical Sciences and Public Health, Marche Polytechnic University, Ancona, Italy.

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http://dx.doi.org/10.3389/fpsyt.2022.858234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990956PMC
March 2022

3F-α-pyrrolydinovalerophenone (3F-α-PVP) in vitro human metabolism: Multiple in silico predictions to assist in LC-HRMS/MS analysis and targeted/untargeted data mining.

J Chromatogr B Analyt Technol Biomed Life Sci 2022 Feb 11;1193:123162. Epub 2022 Feb 11.

Marche Polytechnic University, Department of Excellence of Biomedical Sciences and Public Health, Section of Legal Medicine, Unit of Forensic Toxicology, via Tronto 10, 60126, Ancona AN, Italy.

Synthetic cathinones (SCs) constitute a heterogenous class of new psychoactive substances (NPS), structurally related to cathinone. SCs represent the widest NPS class, second to synthetic cannabinoids, accounting for approximately 160 different analogues with substitution at the phenyl group, the amine group, or the alkyl chain. In 2020, α-pyrrolidonophenone analogues were the most trafficked SCs, and were involved in many fatalities and intoxication cases. In particular, 3F-α-pyrrolidinovalerophenone (3F-α-PVP) was the cause of the highest number of SC-related fatal intoxications in Sweden in 2018. Minor structural modifications are used to avoid legal controls and analytical detection, but may also induce different toxicological profile. Therefore, the identification of specific markers of consumption is essential to discriminate SCs in clinical and forensic toxicology. In this study, we assessed 3F-α-PVP metabolic profile. 3F-α-PVP was incubated with 10-donor-pooled human hepatocytes, LC-HRMS/MS analysis, and software-assisted data mining. This well-established workflow was completed by in silico metabolite predictions using three different freeware. Ten metabolites were identified after 3 h incubation, including hydrogenated, hydroxylated, oxidated, and N-dealkylated metabolites. A total of 51 phase I and II metabolites were predicted, among which 7 were detected in the incubations. We suggest 3F-α-PVP N-butanoic acid, 3F-α-PVP pentanol, and 3F-α-PVP 2-ketopyrrolidinyl-pentanol as specific biomarkers of 3F-α-PVP consumption. This is the first time that an N-ethanoic acid is detected in the metabolic pathway of a pyrrolidine SC, demonstrating the importance of a dual targeted/untargeted data mining strategy.
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http://dx.doi.org/10.1016/j.jchromb.2022.123162DOI Listing
February 2022

The effects of the COVID-19 pandemic on the use of the performance-enhancing drugs.

Acta Biomed 2022 01 19;92(6):e2021401. Epub 2022 Jan 19.

School of Law, Università politecnica delle Marche di Ancona, Italy.

The coronavirus disease (COVID-19) pandemic has been impacting the whole society in every aspect of the daily life, comprising the sport field. Several restrictive strategies have been implemented by governments in an effort to stem the spread of the disease and salvage public health. Such efforts have severely constrained access to non-essential services, leading to the closure of non-essential points of gathering and business and the enforcement of rigorous social distancing and prolonged lockdowns, in addition to masking and stay-at-home mandates. However necessary, there is no denying that such extremely rigorous, and to most people unprecedented, measures have adversely affected the global economy and the daily lives of everyone of us, including professional and amateur athletes (1). The most important sport events were postponed or cancelled, including the 2020 Tokyo Olympic Games. But how was the phenomenon of performance-enhancing drug (PED) use impacted and how was the most concerning issue affecting the integrity of sport affected by the pandemic control restrictions? The World Anti-doping Agency (WADA) was established in 1999, whereas its code was implemented in 2004 in order to articulate and enforce doping control initiatives and provide educational strategies aimed at preventing PED use (2). Nonetheless, it is worth noting that the prevalence of PED use among athletes is mostly unchanged since the foundation of WADA. Unfortunately, the use of the performance-enhancing drugs is not limited to athletic performances, but it concerns other settings as well. Nowadays, several strategies for doping control are adopted such as education, deterrence, detection, enforcement and rule of law (3), but the most important anti-dissemination strategy is constituted by information campaigns, especially addressed to youngsters, meant to raise awareness as to the serious health risks involved in PED use. Currently, the primary drivers of anabolic androgenic steroids (ASA) use are 1) the determination to improve performances and prevail no matter what the cost may be; 2) the economic benefits, popularity and fame; 3) greater stamina and resistance. This public health issue has raised particular concerns due to the recent ASA market developments, which is somewhat similar to the illicit market of narcotic drugs. Moreover, it has to be considered that the higher stress and psychosocial condition related to pandemic social restrictions has fueled and exacerbated substance use disorders (4). The prevalence of doping in sport causes unfairness and damages the very fabric of our society, especially insofar as it involves children and young adults who look up to athletes as role models. In this concern, the impact of the COVD-19 pandemic may have led to substantial modifications in substance use patterns and an increased risk of substitution, adulteration, contamination, and dilution with a potentially harmful substance (5, 6). During the COVID-19 lockdown, WADA and stakeholders suspended or scaled down doping control programs, testing and other activities. As a consequence, athletes have seen the unexpected opportunity to misuse AAS without the possible risk of testing positive (7). This has been controversial, considering the measures taken by governments to flatten the pandemic curve in order to safeguard public health. Indeed, all the technologies implemented for teleworking, such as teaching students on-line, telehealth applications, prescriptions and referrals, and treating patients in hospitals/care homes via video links can also be applied to enhance and uphold sport integrity. Conversely, anti-doping testing for professional competitive athletes has increased, due to the lockdown raising suspicion about doping opportunities. The U.S. Anti-doping Agency has put in place novel measures to combat the lack of anti-doping testing during the pandemic: these include a "in-home self-test" that requires athletes to provide urine and small blood samples at home to be tested in the anti-doping laboratory, under supervision provided by video-conference (8). As such, reports from forensic science and toxicology laboratories are crucial for the early detection and response to such events. Furthermore, toxicology laboratories should assure their continue effort in providing new methods and technologies designed to tackle the consumption of illicit substances and to monitor the constantly changing illegal drug markets (9). The most recent WADA code revision has certainly brought about important progress in the ongoing fight against PED abuse. Indeed, it has introduced the possibility to store the samples for 10 years after the first analysis, maintaining the same legal value if re-tested and use for prosecution purposes (10). In that regard, the prospect of re-testing the same sample with newly developed analytical methods based on innovative technologies may represent a strong deterrent for doping users, since anti-doping research rapidly evolves (6), largely by implementing the same approaches used to fight new psychoactive substances (NPS) use (11,12). It is worth noting that the NPS phenomenon bears several similarities with doping, especially due to the constant emergence of new substances and methods aimed at circumventing current legal restrictions. In Italy, the National Antidoping Organization (NADO-Italia) is in charge of guaranteeing compliance with WADA rules and the transposition of the List of Prohibited Substances and Methods. However, the gap between elite athletes and amateur athletes is still broad and unaddressed, since non-professional sport competitions are not adequately overseen, and neither are the competing athletes . This difference may give rise to an important public health issue, on account of the adverse effects of uncontrolled doping agents consumption. In this concern, the Italian anti-doping law created the "Section of the Technical Health Committee for Supervision and Control on Doping and for Health Protection in Sport Activities", that carries out, among its other tasks, the following activities on amateur sport: 1) updating each year the list of banned substances and practices, adapting it to the WADA list; 2) determining cases, criteria and methodologies for anti-doping controls; 3) promoting research projects and information/training campaigns meant to protect health in sports and tackle doping (13). In conclusion, regarding the highly complex dynamics triggered by the pandemic, new and unexpected challenges have come to the fore in the ongoing fight against substance abuse in its every aspect, such as NPS (14), ASA consumption by amateur athletes, or other substance abuse settings, e.g. driving under the influence of psychotropic substances (15). The current Italian antidoping approach for amateur athletes seems to be a promising strategy to bridge the gap between professional sports and amateur sports. Moreover, youngsters should be thoroughly educated as to the threats posed by such substances, so that they can realize how profoundly and severely drug abuse can affect not only their sport career, but their health and well-being overall.
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http://dx.doi.org/10.23750/abm.v92i6.12377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823578PMC
January 2022

In silico prediction, LC-HRMS/MS analysis, and targeted/untargeted data-mining workflow for the profiling of phenylfentanyl in vitro metabolites.

Talanta 2021 Dec 28;235:122740. Epub 2021 Jul 28.

Unit of Forensic Toxicology, Section of Legal Medicine, Department of Excellence of Biomedical Sciences and Public Health, Marche Polytechnic University, 60126, Ancona, Italy; Unit of Forensic Toxicology, Section of Legal Medicine, Department of Anatomical, Histological, Forensic, and Orthopedic Sciences, Sapienza University of Rome, 00198, Rome, Italy.

Illicit fentanyl and analogues have been involved in many fatalities and cases of intoxication across the United States over the last decade, and are becoming a health concern in Europe. New potent analogues emerge onto the drug market every year to circumvent analytical detection and legislation, and little pharmacological/toxicological data are available when the substances first appear. However, pharmacokinetic data are crucial to determine specific biomarkers of consumption in clinical and forensic settings, considering the low active doses and the rapid metabolism of fentanyl analogues. Phenylfentanyl is a novel analogue that was first detected in seized material in 2017, and little is currently known about this substance and its metabolism. We studied phenylfentanyl metabolic fate using in silico predictions with GLORYx freeware, human hepatocyte incubations, and liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS). We applied a specific targeted/untargeted workflow using data-mining software to allow the rapid and partially automated screening of LC-HRMS/MS raw data. Approximately 90,000 substances were initially individuated after 3-h incubation with hepatocytes, and 115 substances were automatically selected for a manual check by the operators. Finally, 13 metabolites, mostly produced by N-dealkylation, amide hydrolysis, oxidation, and combinations thereof, were identified. We suggest phenylnorfentanyl as the main biological marker of phenylfentanyl use, and we proposed the inclusion of its fragmentation pattern in mzCloud and HighResNPS online libraries. Other major metabolites include N-Phenyl-1-(2-phenylethyl)-4-piperidinamine (4-ANPP), 1-(2-phenylethyl)-4-piperidinol, and other non-specific metabolites. Phase II transformations were infrequent, and the hydrolysis of the biological samples is not required to increase the detection capability of non-conjugated metabolites. The overall workflow is easily adaptable for the metabolite profiling of other novel psychoactive substances.
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http://dx.doi.org/10.1016/j.talanta.2021.122740DOI Listing
December 2021

Editorial: New Trends of Substance Abuse: Looking for New Psychotropic Effects of Chem Sex Drugs, Cognitive Enhancers, and New Psychoactive Substances.

Front Psychiatry 2020 23;11:612192. Epub 2020 Nov 23.

Unit of Forensic Toxicology, Section of Legal Medicine, Department of Anatomical, Histological, Forensic, and Orthopedic Sciences, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.3389/fpsyt.2020.612192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719771PMC
November 2020

Disposition of Cannabidiol Metabolites in Serum and Urine from Healthy Individuals Treated with Pharmaceutical Preparations of Medical Cannabis.

Pharmaceuticals (Basel) 2020 Dec 12;13(12). Epub 2020 Dec 12.

Clinical Pharmacology Unit, Hospital Universitari Germans Trias i Pujol and Institut de Recerca Germans Trias i Pujol (HUGTiP-IGTP), 08916 Badalona, Spain.

The use of cannabis flowering tops with standardized amounts of active phytocannabinoids was recently authorized in several countries to treat several painful pathological conditions. The acute pharmacological effects and disposition of Δ-9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors and THC metabolites after oil and decoction administration have been already described. In this study, the disposition of CBD metabolites: 7-carboxy-cannabidiol (7-COOH-CBD), 7-hydroxycannabidiol (7-OH-CBD), 6-α-hydroxycannabidiol (6-α-OH-CBD), and 6-β-hydroxycannabidiol (6-β-OH-CBD) in the serum and urine of healthy volunteers was presented. Thirteen healthy volunteers were administered 100 mL of cannabis decoction in the first experimental session and, after 15 days of washout, 0.45 mL of oil. Serum and urine samples were collected at different time points, and the CBD metabolites were quantified by ultra-high-performance liquid chromatography-tandem mass spectrometry. The most abundant serum metabolite was 7-COOH-CBD, followed by 7-OH-CBD, 6-β-OH-CBD, and6-α-OH-CBD, after decoction and oil. Both 7-OH-CBD and the 6-α-OH-CBD showed similar pharmacokinetic properties following administration of both cannabis preparations, whereas 7-COOH and 6-α-OH-CBD displayed a significant higher bioavailability after decoction consumption. All CBD metabolites were similarly excreted after oil and decoction intake apart from 6-α-OH-CBD, which had a significantly lower excretion after oil administration. The pharmacokinetic characterization of CBD metabolites is crucial for clinical practice since the cannabis herbal preparations are increasingly used for several pathological conditions.
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http://dx.doi.org/10.3390/ph13120459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763054PMC
December 2020

A Review of Synthetic Cathinone-Related Fatalities From 2017 to 2020.

Ther Drug Monit 2021 02;43(1):52-68

Institute of Emerging Health Professions, Thomas Jefferson University, Philadelphia, Pennsylvania.

Background: Synthetic cathinones (SCs) are designer analogs of the natural active principle of khat. Since their appearance on the black market in 2003, their popularity has increased annually, and they have become the most seized class of new psychoactive substances reported to the UNODC Early Warning Advisory system. The constant introduction of newly synthesized molecules makes this issue difficult to monitor. The authors reviewed the most recent SC-related fatalities worldwide to highlight new trends of consumption, reporting acute pharmacological and toxicological symptoms, scene investigations, analytical methods, and reported SC concentrations in diverse biological matrices.

Methods: A literature search was performed using scientific databases such as PubMed, Scopus, Science Direct, Web of Science, and Research Gate to identify relevant scientific publications from 2017 to 2020. In addition, a search was conducted through the EU EWS.

Results: From 2017 to 2020, 31 different SCs were identified in 75 reported fatal intoxications in the literature, alone or in combination with other substances. The most abused SCs were N-ethylpentylone, N-ethylhexedrone, and 4-chloromethcathinone. The EU EWS included less detail on 72 additional SC-related fatalities from 2017 to 2020.

Conclusions: New SCs continuously replace older natural and synthetic stimulant drugs, making determining the cause of death difficult. Analytical methods and high-performance mass spectrometry instruments are essential to detect the low concentrations of these potent new SCs. Little data are available on the pharmacology of these new drugs; the evaluation of toxicological antemortem and postmortem findings provides critical data on the drug's pharmacology and toxicology and for the interpretation of new SC cases.
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http://dx.doi.org/10.1097/FTD.0000000000000808DOI Listing
February 2021

A Comprehensive HPLC-MS-MS Screening Method for 77 New Psychoactive Substances, 24 Classic Drugs and 18 Related Metabolites in Blood, Urine and Oral Fluid.

J Anal Toxicol 2020 Dec;44(8):769-783

Department of Excellence of Biomedical Sciences and Public Health, University "Politecnica delle Marche" of Ancona, Via Tronto 71, 60124, Ancona, Italy.

To date, more than 800 molecules are classified as New Psychoactive Substances (NPS), and it is reported that this number increases every year. Whereas several cases of polydrug consumption that led to acute intoxication and death are reported, a lack of effective analytical screening method to detect NPS and classical drug of abuse in human matrices affects the prompt identification of the probable cause of intoxication in emergency department of hospitals. In this concern, a fast, simple and comprehensive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) screening method to detect and quantify 77 NPS, 24 classic drugs and 18 related metabolites has been successfully developed and validated in blood, urine and oral fluid. A small volume (100 µL) of whole blood samples spiked with internal standard deuterated mixture was added to 70 µL of M3® buffer, and after precipitation of blood proteins, the supernatant was evaporated to dryness and reconstituted in 1 mL of mobile phase. Same volume (100 µL) of urine and oral fluid samples spiked with internal standard deuterated mix were only diluted with 500 µL of M3® reagent. One microliter of samples of each matrix was injected into HPLC-MS-MS equipment. The run time lasted 10 min with a gradient mobile phase. Mass spectrometric analysis was performed in positive ion multiple reaction monitoring mode. The method was linear for all analytes under investigation with a determination coefficient always better than 0.99. The calibration range for blood and oral fluid was from limits of quantification (LOQs) to 200 ng/mL, whereas that for urine was LOQs to 1000 ng/mL. Recovery and matrix effect were always higher than 80%, whereas intra-assay and inter-assay precision were always better than 19% and accuracy was always within 19% of target in every matrix. Applicability of the method was verified by analysis of samples from real cases.
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http://dx.doi.org/10.1093/jat/bkaa103DOI Listing
December 2020

Development and validation of fast UHPLC-MS/MS screening method for 87 NPS and 32 other drugs of abuse in hair and nails: application to real cases.

Anal Bioanal Chem 2020 Aug 15;412(21):5125-5145. Epub 2020 Feb 15.

Department of Excellence of Biomedical Sciences and Public Health, University "Politecnica delle Marche" of Ancona, Via Conca 71, 60124, Ancona, Italy.

Interest on keratinized matrix analysis for clinical and forensic purposes has been recently grown due to the wide temporary detection window for psychotropic and toxic substances entrapped after repeated consumption. The aim of this study was the development and full validation of an UHPLC-MS/MS screening method to quantify 119 molecules among most abused classic drugs and new psychoactive substances in hair and in nails, to assess the polyconsumption. Twenty-five milligrams of hair or nail samples, added with the internal standard mixture, were cut and incubated with 500 μL M3® buffer reagent at controlled temperature. After cooling, 1 μL supernatant was injected in the chromatographic system equipped with an Oasis HLB column. After the 10 min chromatographic separation through a gradient mobile phase (aqueous ammonium formate, phase A; acetonitrile, phase B), the target compounds were detected in multiple reaction monitoring mode. The method was linear (r always better than 0.99) in a calibration range of LOQ 20000 pg compound for milligram hair and of LOQ 1000 pg compound per milligram nail. Process efficiency of analytes under investigation was always better than 65% and no significant ion suppression due to matrix effect was observed. Intra-assay and inter-assay precision and accuracy were always better than 15%. The applicability and trueness of the method were examined by analysing real samples of hair and nail from users of psychoactive drugs in recreational contexts. Both classic drugs and new psychoactive substances could be determined as result of single or repeated use and accumulation in keratin matrices. Graphical abstract.
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http://dx.doi.org/10.1007/s00216-020-02462-6DOI Listing
August 2020

Testing Unconventional Matrices to Monitor for Prenatal Exposure to Heroin, Cocaine, Amphetamines, Synthetic Cathinones, and Synthetic Opioids.

Ther Drug Monit 2020 04;42(2):205-221

Section of Legal Medicine, Università Politecnica delle Marche, Ancona, Italy.

Background: The prevalence of drug use during pregnancy continues to increase despite the associated serious adverse obstetrical outcomes, including increased risk of miscarriage, fetal growth restriction, brain development impairment, neonatal abstinence syndrome, preterm delivery, and stillbirths. Monitoring drug use during pregnancy is crucial to limit prenatal exposure and provide suitable obstetrical health care. The authors reviewed published literature reporting the concentrations of common drugs of abuse and new psychoactive substances (NPS), such as synthetic cathinones and synthetic opioids, NPS, and their metabolites using unconventional matrices to identify drug use during pregnancy and improve data interpretation.

Methods: A literature search was performed from 2010 to July 2019 using PubMed, Scopus, Web of Science scientific databases, and reports from international institutions to review recently published articles on heroin, cocaine, amphetamine, methamphetamine, synthetic cathinone, and synthetic opioid monitoring during pregnancy.

Results: Meconium has been tested for decades to document prenatal exposure to drugs, but data regarding drug concentrations in amniotic fluid, the placenta, the umbilical cord, and neonatal hair are still lacking. Data on prenatal exposure to NPS are limited.

Conclusions: Maternal hair testing is the most sensitive alternative matrix for identifying drug use during pregnancy, while drug concentrations in the meconium, placenta, and umbilical cord offer the identification of prenatal drug exposure at birth. Adverse developmental outcomes for the infant make it critical to promptly identify maternal drug use to limit fetal exposure or, if determined at birth, to provide resources to the exposed child and family. Alternative matrices offer choices for monitoring and challenge laboratories to deliver highly sensitive and specific analytical methods for detection.
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http://dx.doi.org/10.1097/FTD.0000000000000719DOI Listing
April 2020

Biomedical analysis of New Psychoactive Substances (NPS) of natural origin.

J Pharm Biomed Anal 2020 Feb 30;179:112945. Epub 2019 Oct 30.

Department of Excellence of Biomedical Sciences and Public Health, University "Politecnica delle Marche" of Ancona, Via Tronto 71, Ancona, Italy. Electronic address:

New psychoactive substances (NPS) can be divided into two main groups: synthetic molecules and active principles of natural origin. With respect to this latter group, a wide range of alkaloids contained in plants, mainly from Asia and South America, can be included in the class of NPS of natural origin. The majority NPS of natural origin presents stimulant and/or hallucinogenic effects (e.g. Catha edulis and Ayahuasca, respectively) while few of them show sedative and relaxing properties (e.g. kratom). Few information is available in relation to the analytical identification of psychoactive principles contained in the plant material. Moreover, to our knowledge, scarce data are present in literature, about the characterization and quantification of the parent drug in biological matrices from intoxication and fatality cases. In addition, the metabolism of natural active principles has not been yet fully investigated for most of the psychoactive substances from plant material. Consequently, their identification is not frequently performed and produced metabolites are often unknown. To fill this gap, we reviewed the currently available analytical methodologies for the identification and quantification of NPS of natural origin in plant material and, whenever possible, in conventional and non-conventional biological matrices of intoxicated and dead subjects. The psychoactive principles contained in the following plants were investigated: Areca catechu, Argyreia nervosa, Ayahuasca, Catha edulis, Ipomoea violacea, Mandragora officinarum, Mitragyna speciosa, Pausinystalia yohimbe, Piper methisticum, Psilocybe, Rivea corymbosa, Salvia divinorum, Sceletium tortuosum, Lactuca virosa. From the results obtained, it can be evidenced that although several analytical methods for the simultaneous quantification of different molecules from the same plants have been developed and validated, a comprehensive method to detect active compounds from different natural specimens both in biological and non-biological matrices is still lacking.
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http://dx.doi.org/10.1016/j.jpba.2019.112945DOI Listing
February 2020

Monitoring Prenatal Exposure to Buprenorphine and Methadone.

Ther Drug Monit 2020 04;42(2):181-193

Unit of Forensic Toxicology, Department of Anatomical, Histological, Forensic, and Orthopedic Sciences, Università la Sapienza, Rome, Italy.

Purpose: Buprenorphine and methadone are international gold standards for managing opioid use disorders. Although they are efficacious in treating opioid dependence, buprenorphine and methadone present risks, especially during pregnancy, causing neonatal abstinence syndrome and adverse obstetrical outcomes. Buprenorphine and methadone are also abused during pregnancy, and identifying their use is important to limit unprescribed prenatal exposure. Previous studies have suggested that concentrations of buprenorphine, but not methadone markers in unconventional matrices may predict child outcomes, although currently only limited data exist. We reviewed the literature on concentrations of buprenorphine, methadone, and their metabolites in unconventional matrices to improve data interpretation.

Methods: A literature search was conducted using scientific databases (PubMed, Scopus, Web of Science, and reports from international institutions) to review published articles on buprenorphine and methadone monitoring during pregnancy.

Results: Buprenorphine and methadone and their metabolites were quantified in the meconium, umbilical cord, placenta, and maternal and neonatal hair. Methadone concentrations in the meconium and hair were typically higher than those in other matrices, although the concentrations in the placenta and umbilical cord were more suitable for predicting neonatal outcomes. Buprenorphine concentrations were lower and required sensitive instrumentation, as measuring buprenorphine glucuronidated metabolites is critical to predict neonatal outcomes.

Conclusions: Unconventional matrices are good alternatives to conventional ones for monitoring drug exposure during pregnancy. However, data are currently scarce on buprenorphine and methadone during pregnancy to accurately interpret their concentrations. Clinical studies should be conducted with larger cohorts, considering confounding factors such as illicit drug co-exposure.
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http://dx.doi.org/10.1097/FTD.0000000000000693DOI Listing
April 2020

Sensitive and reliable gas chromatography tandem mass spectrometry assay for ethyl glucuronide in neonatal meconium.

J Pharm Biomed Anal 2019 Oct 6;175:112743. Epub 2019 Jul 6.

Section of Legal Medicine, Dept. of Excellence-Biomedical Sciences and Public Health, Ancona, Italy. Electronic address:

Prenatal exposure to maternal ethanol leads to serious physical and mental irreversible disabilities. Ethyl glucuronide (EtG) is a direct metabolite of alcohol and its measurement in neonatal meconium has been established as the best biomarker to assess prenatal exposure to social and excessive gestational ethanol. We developed and validated the first gas chromatography tandem mass spectrometry method to quantify EtG extracted from meconium by a simple solid phase extraction pretreatment. The method was linear from limit of quantification (2 ng/g) to 200 ng/g matrix with good determination coefficient (r = 0.99). Recovery of EtG from meconium was always higher than 70% and intra-assay and inter-assay precision and accuracy were always better than 10%. Robustness of the developed GC-MS/MS method was tested by analysing 150 real samples coming from a previous national epidemiological project pre-screened through an ultra-chromatography tandem mass spectrometry assay obtaining a good comparability of results obtained by the two methods.
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http://dx.doi.org/10.1016/j.jpba.2019.06.040DOI Listing
October 2019

Is etizolam a safe medication? Effects on psychomotor perfomance at therapeutic dosages of a newly abused psychoactive substance.

Forensic Sci Int 2019 Aug 18;301:137-141. Epub 2019 May 18.

Section of Legal Medicine, Università Politecnica delle Marche, Ancona, Italy.

Etizolam is a drug from the thienotriazoldiazepine class, widely prescribed as anxiolytic due to its apparently secure toxicological profile. Nevertheless, some recent cases of etizolam dependence, intoxications and fatalities associated to its abuse have been reported in the international literature. For this reason, the drug listed as new psychoactive substance (NPS) by the World Health Organization (WHO) since 2015. Euphoric effect at high dosage is the first cause of its recreational use that has determined a wider distribution in the illicit market. An experimental study was performed to obtain evidence that etizolam at low therapeutic dosages is a drug with negligible influence on the psychomotor performances involved in driving. The psychomotor performance was assessed by performing different tests, such as critical tracking task (CTT), critical flicker fusion (CFF), choice reaction time (CRT), visual vigilance task (VVT), response competition test (RCT) in a group of 16 healthy volunteers after a single administration of etizolam at two different dosages (0.25 mg or 1.00 mg) in comparison to placebo. The test results showed that etizolam at 0.25 mg and 1.00 mg had no significant effect on vigilance, short term memory, psychomotor coordination or speed in decision making. Differently, abuse of etizolam to obtain the euphoric effects at presumably high dosages or in combination with other psychoactive substances could be fatal. The negligible side effects on mental and behavioral function demonstrated by this study, could represent an incitement to abuse, which can be strongly discouraged with correct information on differences between its correct use and its misuse.
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http://dx.doi.org/10.1016/j.forsciint.2019.05.018DOI Listing
August 2019
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