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Strano Rossi S.,Catholic University of the Sacred Heart | Anzillotti L.,Catholic University of the Sacred Heart | Castrignano E.,Catholic University of the Sacred Heart | Frison G.,Laboratory of Environmental Hygiene and Forensic Toxicology | And 2 more authors.
Drug Testing and Analysis | Year: 2014

Zolpidem and zopiclone (Z-compounds) are non-benzodiazepine hypnotics of new generation that can be used in drug-facilitated sexual assault (DFSA). Their determination in biological fluids, mainly urine, is of primary importance; nevertheless, although they are excreted almost entirely as metabolites, available methods deal mainly with the determination of the unmetabolized drug. This paper describes a method for the determination in urine of Z-compounds and their metabolites by ultra-high-pressure liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) and UHPLC coupled with high resolution/high accuracy Orbitrap® mass spectrometry (UHPLC-HRMS). The metabolic profile was studied on real samples collected from subjects in therapy with zolpidem or zopiclone; the main urinary metabolites were identified and their MS behaviour studied by MS/MS and HRMS. Two carboxy- and three hydroxy- metabolites, that could be also detected by gas chromatography/mass spectrometry (GC-MS) as trimethylsylyl derivatives, have been identified for zolpidem. Also, at least one dihydroxilated metabolite was detected. As for zopiclone, the two main metabolites detected were N-demethyl and N-oxide zopiclone. For both substances, the unmetabolized compounds were excreted in low amounts in urine. In consideration of these data, a UHPLC-MS/MS method for the determination of Z-compounds and their main metabolites after isotopic dilution with deuterated analogues of zolpidem and zopiclone and direct injection of urine samples was set up. The proposed UHPLC-MS/MS method appears to be practically applicable for the analysis of urine samples in analytical and forensic toxicology cases, as well as in cases of suspected DFSA. © 2013 John Wiley & Sons, Ltd.


Frison G.,Laboratory of Environmental Hygiene and Forensic Toxicology | Odoardi S.,Catholic University of the Sacred Heart | Frasson S.,Laboratory of Environmental Hygiene and Forensic Toxicology | Sciarrone R.,Laboratory of Environmental Hygiene and Forensic Toxicology | And 4 more authors.
Rapid Communications in Mass Spectrometry | Year: 2015

Rationale We describe the analytical characterization of the designer drug bk-2C-B, a cathinone derivative, contained in a seized tablet, in the absence of an analytical standard. Methods The analytical techniques employed include gas chromatography/mass spectrometry (GC/MS), without and with derivatization with 2,2,2-trichloroethyl chloroformate, liquid chromatography/high-resolution-MS (LC/HRMS) with an Orbitrap® analyzer, and nuclear magnetic resonance (NMR). LC/HRMS measurements consisted of accurate mass measurements of MH+ ionic species under full scan conditions; comparison of experimental and calculated MH+ isotopic patterns; examination of the isotopic fine structure (IFS) of the M+1, M+2, M+3 isotopic peaks relative to the monoisotopic M+0 peak; study of MH+ collision-induced dissociation (CID) product ions obtained in fragmentation experiments. Results GC/MS analysis gave highly informative EI mass spectra, particularly after the derivatization of bk-2C-B with 2,2,2-trichloroethyl chloroformate. The application of LC/HRMS, allowing for accurate mass measurements at 100,000 resolving power, greatly enhanced analytical capabilities in structural characterization of this new designer drug. HRMS allowed us to obtain the accurate mass measurements of bk-2C-B MH+ ionic species, with a mass accuracy of 2.19 ppm; fully superimposable experimental and calculated MH+ isotopic patterns, with RIA1 and RIA2 values <4%; the IFS of the M+1, M+2, M+3 isotopic peaks relative to the monoisotopic M+0 peak completely in accordance with theoretical values. These findings enabled us to obtain the elemental composition formula of the seized drug. Furthermore, characteristic MH+ CID product ions enabled the characterization of the bk-2C-B molecular structure. The presence of 79Br and 81Br isotopes in the substance molecule produced a characteristic isotopic pattern in most MS spectra. Lastly, NMR spectra allowed us to obtain useful information about the position of substituents in the designer drug. Conclusions The combination of all the analytical techniques employed allowed the characterization of the seized psychoactive substance, in spite of the lack of a reference standard. Copyright © 2015 John Wiley & Sons, Ltd.


Frison G.,Laboratory of Environmental Hygiene and Forensic Toxicology | Zamengo L.,Laboratory of Environmental Hygiene and Forensic Toxicology | Zancanaro F.,Laboratory of Environmental Hygiene and Forensic Toxicology | Tisato F.,CNR Institute of Neuroscience | Traldi P.,CNR Institute of Neuroscience
Rapid Communications in Mass Spectrometry | Year: 2016

Rationale Clinical and forensic toxicology laboratories are challenged every day by the analytical aspects of the new psychoactive substances phenomenon. In this study we describe the analytical characterization of a new ketamine derivative, deschloroketamine (2-methylamino-2-phenylcyclohexanone), contained in seized powders. Methods The analytical techniques employed include gas chromatography/mass spectrometry (GC/MS), liquid chromatography/electrospray ionization coupled with Orbitrap high-resolution/MS (LC/ESI-HRMS), multistage MS (ESI-MSn), and NMR. The LC/ESI-HRMS analyses consisted of accurate mass measurements of MH+ ions in full-scan mode; comparison of experimental and calculated MH+ isotopic patterns; and examination of the isotopic fine structure (IFS) of the M + 1, M + 2, M + 3 isotopic peaks relative to the monoisotopic M + 0 peak. The collision-induced product ions of the MH+ ions were studied by both HRMS and MSn. 1H and 13C NMR measurements were carried out to confirm the chemical structure of the analyte. Results The EI mass spectra obtained by GC/MS analysis showed the presence of molecular ions at m/z 203, and main fragment ions at m/z 175, 174, 160, 147, 146, and 132. The application of LC/ESI-HRMS allowed us to obtain: the accurate mass of deschloroketamine MH+ ions with a mass accuracy of 1.47 ppm; fully superimposable experimental and calculated MH+ isotopic patterns, with a relative isotopic abundance value of 3.69 %; and the IFS of the M + 1, M + 2, M + 3 isotopic peaks completely in accordance with theoretical values. Examination of the product ions of MH+, as well as the study of both 1H and 13C NMR spectra, enabled the full characterization of the molecular structure of deschloroketamine. Conclusions The combination of the employed analytical techniques allowed the characterization of the seized psychoactive substance, in spite of the lack of a reference standard. Deschloroketamine is a ketamine analogue considered to be more potent and longer lasting than ketamine, and this paper is probably the first to report on its analytical characterization. Copyright © 2015 John Wiley & Sons, Ltd.


Zamengo L.,Laboratory of Environmental Hygiene and Forensic Toxicology | Frison G.,Laboratory of Environmental Hygiene and Forensic Toxicology | Tedeschi G.,Laboratory of Environmental Hygiene and Forensic Toxicology | Frasson S.,Laboratory of Environmental Hygiene and Forensic Toxicology
Forensic Science International | Year: 2016

Blood alcohol concentration is the most frequent analytical determination carried out in forensic toxicology laboratories worldwide. It is usually required to assess if an offence has been committed by comparing blood alcohol levels with specified legal limits, which can vary widely among countries. Due to possible serious legal consequences associated with non-compliant alcohol levels, measurement uncertainty should be carefully evaluated, along with other metrological aspects which can influence the final result. The whole procedure can be time-consuming and error-generating in routine practice, increasing the risks for unreliable assessments. A software application named Ethanol WorkBook (EtWB) was developed at the author's laboratory by using Visual Basic for Application language and MS Excel®, with the aim of providing help to forensic analysts involved in blood alcohol determinations. The program can (i) calculate measurement uncertainties and decision limits with different methodologies; (ii) assess compliance to specification limits with a guard-band approach; (iii) manage quality control (QC) data and create control charts for QC samples; (iv) create control maps from real cases data archives; (v) provide laboratory reports with graphical outputs for elaborated data and (vi) create comprehensive searchable case archives. A typical example of drink driving case is presented and discussed to illustrate the importance of a metrological approach for reliable compliance assessment and to demonstrate software application in routine practice. The tool is made freely available to the scientific community at request. © 2016 Elsevier Ireland Ltd.


Zamengo L.,Laboratory of Environmental Hygiene and Forensic Toxicology | Frison G.,Laboratory of Environmental Hygiene and Forensic Toxicology | Bettin C.,Laboratory of Environmental Hygiene and Forensic Toxicology | Sciarrone R.,Laboratory of Environmental Hygiene and Forensic Toxicology
Drug Testing and Analysis | Year: 2014

Cannabis is the most widely used illicit substance globally, with an estimated annual prevalence in 2010 of 2.6-5.0% of the adult population. Concerns have been expressed about increases in the potency of cannabis products. A high tetrahydrocannabinol (THC) content can increase anxiety, depression, and psychotic symptoms, and can increase the risk of dependence and adverse effects on the respiratory and cardiovascular systems in regular users. The aim of this study was to report statistical data about the potency of cannabis products seized in the north-east of Italy, in a geographical area centred in Venice and extending for more than 10 000km2 with a population of more than two million, by investigating the variability observed in THC levels of about 4000 samples of cannabis products analyzed over the period 2010-2012. Overall median THC content showed an increasing trend over the study period from about 6.0% to 8.1% (6.2-8.9% for cannabis resin, 5.1-7.6% for herbal cannabis). The variation in the THC content of individual samples was very large, ranging from 0.3% to 31% for cannabis resin and from 0.1 to 19% for herbal cannabis. Median CBN:THC ratios showed a slightly decreasing trend over the study period, from 0.09 (2010) to 0.03 (2012), suggesting an increasing freshness of submitted materials. Median CBD:THC ratios also showed a decreasing trend over the study from about 0.52 (2010) to 0.18 (2012), likely due to the increase in submissions of materials from indoor and domestic cultivation with improved breeding methods. © 2013 John Wiley & Sons, Ltd.

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