Congratulations to Dr. Baselt for the publication of his 10th edition and the expansion of his classic toxicology text to cover over 1,500 medications and chemicals. This enduring work provides a c...

Disposition of Toxic Drugs and Chemicals in Man

This review paper covers the forensic-relevant literature in controlled substances from 2016 to 2019 as a part of the 19th Interpol International Forensic Science Managers Symposium. The review papers are also available at the Interpol website at: https://www.interpol.int/content/download/14458/file/Interpol%20Review%20Papers%202019.pdf.

Interpol review of controlled substances 2016–2019

Among the phencyclidine (PCP) and synthetic cathinone analogs present on the street market, 3-methoxyphencyclidine (3-MeO-PCP) is one of the most popular dissociative hallucinogen drugs, while 3-methylmethcathinone (3-MMC) is a commonly encountered psychostimulant. Numerous 3-MeO-PCP- and 3-MMC-related intoxication cases have been reported worldwide. Identification of the positional isomers of MeO-PCP and MMC families are particularly challenging for clinical and forensic laboratories; this is mostly due to their difficult chromatographic separation (particularly when using liquid chromatography-LC) and similar mass spectrometric behaviors. 3-MeO-PCP and 3-MMC were identified in two powders, detained by two subjects and seized by the police, by different analytical techniques, including liquid chromatography-high-resolution accurate-mass Orbitrap mass spectrometry (LC-HRAM-Orbitrap-MS), and solid deposition gas chromatography-Fourier transform infrared spectroscopy (sd-GC-FTIR). LC-HRAM-Orbitrap-MS allowed us to assign the elemental formulae C18H27NO (MeO-PCP) and C11H15NO (MMC) through accurate mass measurement of the two MH+ ions, and the comparison of experimental and calculated MH+ isotopic patterns. However, MH+ collision-induced product ions spectra were not conclusive in discriminating between the positional isomers [(3-MeO-PCP vs. 4-MeO-PCP) and (3-MMC vs. 4-MMC and 2-MMC)]. Likewise, sd-GC-FTIR easily allowed us to differentiate between the MeO-PCP and MMC positional isomers unambiguously, confirming the presence of 3-MeO-PCP and 3-MMC, due to the high-quality match factor of the experimental FTIR spectra against the target FTIR spectra of MeO-PCP and MMC isomers in a dedicated library. 3-MeO-PCP (in contrast to 3-MMC) was also detected in blood and urine samples of both subjects and analyzed in the context of routine forensic casework by LC-HRAM-Orbitrap-MS following a simple deproteinization step. In addition, this untargeted approach allowed us to detect dozens of phase I and phase II 3-MeO-PCP metabolites in all biological specimens. Analysis of the extracted samples by sd-GC-FTIR revealed the presence of 3-MeO-PCP, thus confirming the intake of such specific methoxy-PCP isomer in both cases. These results highlight the effectiveness of LC-HRAM-Orbitrap-MS and sd-GC-FTIR data in attaining full structural characterization of the psychoactive drugs, even in absence of reference standards, in both non-biological and biological specimens.

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Analytical Characterization of 3-MeO-PCP and 3-MMC in Seized Products and Biosamples: The Role of LC-HRAM-Orbitrap-MS and Solid Deposition GC-FTIR.

Aim: The aim of this study was to perform a cross-reactivity investigation of six benzofurans with immunoassays (IAs) screening tests for amphetamines and ecstasy in urine samples. Methods: The following benzofuranes were investigated: 5-(2-Methylaminopropyl)Benzofuran (5-MAPB), 5-(2-methylaminopropyl)-2,3-dihydrobenzofuran (5-MAPDB), 5-(2-Aminopropyl)-Benzofuran (5-APB), 5-(2-Aminopropyl)-2,3-dihydrobenzofuran (5-APDB), 5-(2-Ethylaminopropyl)Benzofuran (5-EAPB) and 5-(2-Aminoethyl)-2,3-dihydrobenzofuran (5-AEDB). The study was performed with urine-free spiked samples and authentic urine samples using eight different IAs for amphetamines and ecstasy. Results: All evaluated benzofurans showed cross-reactivity in some of the IAs tested, except for 5-AEDB. Urine samples of an intoxication case involving 5-MAPB, 5-APB and 5-EAPB were also positives in the IAs tested. Conclusion: There is an important variability in the cross-reactivity of the IAs for amphetamine and ecstasy caused by benzofurans depending on ...

Cross-reactivity of selected benzofurans with commercial amphetamine and ecstasy immunoassays in urine.

Background:Chloroquine and hydroxychloroquine are medical drugs used to treat the chemoprophylaxis of malaria and a second-line anti-inflammatory drug.Methods:We performed a study of cross-reactivity of chloroquine and hydroxychloroquine in the DRI Amphetamine Assay inspired by a case report of a se

Cross-Reactivity of Chloroquine and Hydroxychloroquine With DRI Amphetamine Immunoassay

We present a false-positive result of ecstasy (3,4-methylenedioxy-NN-methylamphetamine) screening due to the therapeutic use of fenofibrate, an antihyperlipidemic drug. Our hypothesis was that the main metabolite of fenofibrate, fenofibric acid, was responsible for this cross-reactivity on a DRI(®) Ecstasy Assay, using a cut-off of 500 ng/mL. We estimated that the addition of 225 µg/mL pure fenofibric acid to blank urine would be sufficient to result in a positive DRI(®) Ecstasy Assay. The results obtained on the urine samples analyses of the patient show that the DRI(®) Ecstasy Assay resulted negative 2 days after discontinuing fenofibrate treatment, when the urine fenofibric acid concentration corrected by creatinine and determinated by gas chromatography-mass spectrometry was 20.3 µg/mg creatinine. The cross-reactivity data for fenofibric acid would seem to indicate that there was insufficient concentration of measured compound to account for the positive immunochemical results for ecstasy. This apparent discrepancy can be explained in several ways, one of them is that the β-glucuronidase-resistent fenofibric acid isomers are responsible. This process could explain the low recovery of free fenofibric acid when we use the developed method for its quantification in urine samples. Positive results on immunoassay screening must be considered presumptive until confirmation with another method based on a different principle, preferably gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry.

Fenofibric Acid Can Cause False-Positive Urine Methylenedioxymethamphetamine Immunoassay Results

Methoxetamine (MXE) and the arylcyclohexylamines 3-methoxy-PCP (3-MeO-PCP) and 4-methoxy-PCP (4-MeO-PCP) are substituted analogs of the dissociative psychoactive substances ketamine and phencyclidine (PCP), respectively. They have emerged on the new psychoactive substances (NPS) market as legal alternatives to these classically banned dissociatives. Little data has been published regarding the cross-reactivity of these NPS in PCP immunoassays (IAs). The aim of this work was to explore the possibilities of detecting 3-MeO-PCP, 4-MeO-PCP, MXE and ketamine in commercial IAs for PCP. The cross-reactivity study was performed in five different PCP IAs using urine-free, spiked samples and urine samples obtained from two 3-MeO-PCP overdose cases. 3-MeO-PCP and 4-MeO-PCP showed cross-reactivity (ranging from 1-143%) in all PCP IAs evaluated. MXE only showed very weak cross-reactivity (ranged from 0.04 to 0.25%) and ketamine was not detected in any PCP IA evaluated. Urine samples from the two overdose cases were positive for PCP in all IAs evaluated. The commercial PCP IAs evaluated exhibited utility as rapid, preliminary screening techniques for 3-MeO-PCP and 4-MeO-PCP, but not for ketamine. The low reactivity of MXE limits its detectability in the PCP IAs evaluated.

Miguel A. Servera

Papers

Cross-Reactivity of Chloroquine and Hydroxychloroquine With DRI Amphetamine Immunoassay

Fenofibric Acid Can Cause False-Positive Urine Methylenedioxymethamphetamine Immunoassay Results

Detectability of Dissociative Psychoactive Substances in Urine by Five Commercial Phencyclidine Immunoassays