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Hans H Maurer - One of the best experts on this subject based on the ideXlab platform.

  • biotransformation and detectability of the Designer Drug 2 5 dimethoxy 4 propylphenethylamine 2c p studied in urine by gc ms lc ms n and lc high resolution ms n
    Analytical and Bioanalytical Chemistry, 2015
    Co-Authors: Carina S D Wink, Alain Turcant, Markus R Meyer, Tina Braun, Hans H Maurer
    Abstract:

    2,5-Dimethoxy-4-propylphenethylamine (2C-P) is a hallucinogenic Designer Drug of the phenethylamine class, the so-called 2Cs, named according to the ethyl spacer between the nitrogen and the aromatic ring. The aims of the present work were to identify the phases I and II metabolites of 2C-P. In addition, the detectability of 2C-P and its metabolites in urine as proof of an intake in clinical or forensic cases was tested. According to the identified metabolites, the following pathways were proposed: N-acetylation; deamination followed by reduction to the corresponding alcohol and oxidation to carbonic acid; mono- and bis-hydroxylation at different positions; mono- and bis-O-demethylation, followed by glucuronidation, sulfation, or both; and combination of these steps. Proof of an intake of a common user’s dose of 2C-P was possible by both standard urine screening approaches, the GC-MS as well as the LC-MS n approach.

  • the in vivo and in vitro metabolism and the detectability in urine of 3 4 methylenedioxy alpha pyrrolidinobutyrophenone mdpbp a new pyrrolidinophenone type Designer Drug studied by gc ms and lc ms n
    Drug Testing and Analysis, 2014
    Co-Authors: Markus R Meyer, Folker Westphal, Sandra Mauer, Golo M J Meyer, Julia Dinger, Birgit Klein, Hans H Maurer
    Abstract:

    3',4'-Methylenedioxy-alpha-pyrrolidinobutyrophenone (MDPBP), a Designer Drug of the pyrrolidinophenone-type, was first seized in Germany in 2009. It was also identified in 'legal high' samples investigated in the UK. Therefore, the aim of the presented work was to identify its in vivo and in vitro phase I and II metabolites using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-ion trap mass spectrometry (LC-MS(n) ). Furthermore, detectability of MDPBP in rat and human urine using standard urine screening approaches (SUSA) by GC-MS and LC-MS(n) was studied. The metabolites were isolated either directly or after enzymatic cleavage of conjugates by solid-phase extraction (C18, HCX). The metabolites were then analyzed and structures proposed after GC-MS (phase I) and LC-MS(n) (phase II). Based on these identified metabolites, the following main metabolic steps could be proposed: demethylenation followed by methylation of one hydroxy group, aromatic and side chain hydroxylation, oxidation of the pyrrolidine ring to the corresponding lactam as well as ring opening to the corresponding carboxylic acid. Furthermore, in rat urine after a typical user's dose as well as in human urine, mainly the metabolites could be detected using the authors' SUSA by GC-MS and LC-MS(n) . Thus, it should be possible to monitor an application of MDPBP assuming similar toxicokinetics in humans. Finally, CYP2C19 and CYP2D6 could be identified as the isoenzymes mainly responsible for demethylenation. Copyright © 2013 John Wiley & Sons, Ltd. Language: en

  • ketamine derived Designer Drug methoxetamine metabolism including isoenzyme kinetics and toxicological detectability using gc ms and lc hr msn
    Analytical and Bioanalytical Chemistry, 2013
    Co-Authors: Markus R Meyer, Martina Bach, Jessica Welter, Michael Bovens, Alain Turcant, Hans H Maurer
    Abstract:

    Methoxetamine (MXE; 2-(3-methoxyphenyl)-2-(N-ethylamino)-cyclohexanone), a ketamine analog, is a new Designer Drug and synthesized for its longer lasting and favorable pharmacological effects over ketamine. The aims of the presented study were to identify the phases I and II metabolites of MXE in rat and human urine by GC-MS and LC-high-resolution (HR)-MS n and to evaluate their detectability by GC-MS and LC-MS n using authors’ standard urine screening approaches (SUSAs). Furthermore, human cytochrome P450 (CYP) enzymes were identified to be involved in the initial metabolic steps of MXE in vitro, and respective enzyme kinetic studies using the metabolite formation and substrate depletion approach were conducted. Finally, human urine samples from forensic cases, where the ingestion of MXE was suspected, were analyzed. Eight metabolites were identified in rat and different human urines allowing postulation of the following metabolic pathways: N-deethylation, O-demethylation, hydroxylation, and combinations as well as glucuronidation or sulfation. The enzyme kinetic studies showed that the initial metabolic step in humans, the N-deethylation, was catalyzed by CYP2B6 and CYP3A4. Both SUSAs using GC-MS or LC-MS n allowed monitoring an MXE intake in urine.

  • studies on the metabolism and detectability of the Designer Drug β naphyrone in rat urine using gc ms and lc hr ms ms
    Drug Testing and Analysis, 2013
    Co-Authors: Markus R Meyer, Denise Prosser, Hans H Maurer
    Abstract:

    Naphyrone (1-naphthalen-2-yl-2-pyrrolidin-1-yl-pentan-1-one; naphthylpyrovalerone, β-naphyrone) is a cathinone Designer Drug and was marketed as replacement for the synthetic cathinone derivative mephedrone. Meanwhile, naphyrone is also classified as a controlled Drug in several countries. Therefore, the aim of this study was to identify the metabolites of naphyrone in rat urine using gas chromatography-mass spectrometry techniques and to show its detectability in urine samples. The following metabolic steps could be detected in rat urine: oxidation of the pyrrolidine ring to the corresponding lactam, hydroxylation of the propyl side chain and the naphthyl ring, degradation to the primary amines after opening of the pyrrolidine ring, and combinations of these steps. Assuming similar kinetics, an intake of naphyrone should be detectable in human urine mainly via its metabolites. Copyright © 2013 John Wiley & Sons, Ltd.

  • new Designer Drug α pyrrolidinovalerophenone pvp studies on its metabolism and toxicological detection in rat urine using gas chromatographic mass spectrometric techniques
    Journal of Mass Spectrometry, 2009
    Co-Authors: Christoph Sauer, Frank T. Peters, Giselher Fritschi, Markus R Meyer, Claudia Haas, Hans H Maurer
    Abstract:

    The aim of the present study was to identify the metabolites of the new Designer Drug α-pyrrolidinovalerophenone (PVP) in rat urine using GC/MS techniques. Eleven metabolites of PVP could be identified suggesting the following metabolic steps: hydroxylation of the side chain followed by dehydrogenation to the corresponding ketone; hydroxylation of the 2 �� position of the pyrrolidine ring followed by dehydrogenation to the corresponding lactam or followed by ring opening to the respective aliphatic aldehyde and further oxidation to the respective carboxylic acid; degradation of the pyrrolidine ring to the corresponding primary amine; and hydroxylation of the phenyl ring, most probably in the 4 � -position. The authors’ screening procedure for pyrrolidinophenones allowed the detection of PVP metabolites after application of a dose corresponding to a presumed user’s dose. In addition, the involvement of nine different human cytochrome P450 (CYP) isoenzymes in the side chain hydroxylation of PVP was investigated and CYP 2B6, 2C19, 2D6, and 3A4 were found to catalyze this reaction. Copyright c � 2009 John Wiley & Sons, Ltd.

Roland F Staack - One of the best experts on this subject based on the ideXlab platform.

  • new Designer Drug 2 5 dimethoxy 4 ethylthio β phenethylamine 2c t 2 studies on its metabolism and toxicological detection in rat urine using gas chromatography mass spectrometry
    Journal of Mass Spectrometry, 2005
    Co-Authors: Denis S Theobald, Roland F Staack, Michael Puetz, Hans H Maurer
    Abstract:

    Studies are described on the metabolism and the toxicological analysis of the phenethylamine-derived Designer Drug 2,5-dimethoxy-4-ethylthio-β-phenethylamine (2C-T-2) in rat urine using gas chromatography/mass spectrometry (GC/MS) after enzymatic cleavage of conjugates, liquid-liquid extraction and derivatization. The structures of 14 metabolites were assigned tentatively by detailed interpretation of their mass spectra. Identification of these metabolites indicated that 2C-T-2 was metabolized by sulfoxidation followed by N-acetylation and either hydroxylation of the S-ethyl side chain or demethylation of one methoxy group, O-demethylation of the parent compound followed by N-acetylation and sulfoxidation, deamination followed by reduction to the corresponding alcohol followed by partial glucuronidation and/or sulfation or by oxidation to the corresponding acid followed either by partial glucuronidation or by degradation to the corresponding benzoic acid derivative followed by partial glucuronidation. Furthermore, 2C-T-2 was metabolized by N-acetylation of the parent compound followed either by O-demethylation and sulfoxidation or by S-dealkylation, S-methylation and sulfoxidation. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS after acid hydrolysis, liquid-liquid extraction microwave-assisted acetylation allowed the detection of an intake of a dose of 2C-T-2 in rat urine, which corresponds to a common Drug users' dose. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of 2C-T-2 in human urine. Copyright © 2005 John Wiley & Sons, Ltd.

  • identification of human cytochrome p450 2d6 as major enzyme involved in the o demethylation of the Designer Drug p methoxymethamphetamine
    Drug Metabolism and Disposition, 2004
    Co-Authors: Roland F Staack, Denis S Theobald, Liane D Paul, Dietmar Springer, Thomas Kraemer, Hans H Maurer
    Abstract:

    p-Methoxymethamphetamine (PMMA) is a new Designer Drug, listed in many countries as a controlled substance. Several fatalities have been attributed to the abuse of this Designer Drug. Previous in vivo studies using Wistar rats had shown that PMMA was metabolized mainly by O-demethylation. The aim of the study presented here was to identify the human hepatic cytochrome P450 (P450) enzymes involved in the biotransformation of PMMA to p-hydroxymethamphetamine. Baculovirus-infected insect cell microsomes, pooled human liver microsomes (pHLMs), and CYP2D6 poor-metabolizer genotype human liver microsomes (PM HLMs) were used for this purpose. Only CYP2D6 catalyzed O-demethylation. The apparent Km and Vmax values in baculovirus-infected insect cell microsomes were 4.6 ± 1.0 μM and 92.0 ± 3.7 pmol/min/pmol P450, respectively, and 42.0 ± 4.0 μM and 412.5 ± 10.8 pmol/min/mg protein in pHLMs. Inhibition studies with 1 μM quinidine showed significant inhibition of the metabolite formation (67.2 ± 0.6%; p

  • new Designer Drug 1 3 4 methylenedioxybenzyl piperazine mdbp studies on its metabolism and toxicological detection in rat urine using gas chromatography mass spectrometry
    Journal of Mass Spectrometry, 2004
    Co-Authors: Roland F Staack, Hans H Maurer
    Abstract:

    Studies are described on the metabolism and toxicological analysis of the piperazine-derived Designer Drug 1-(3,4-methylenedioxybenzyl)piperazine (MDBP) in rat urine using gas chromatography/mass spectrometry (GC/MS). The identified metabolites indicated that MDBP was metabolized by demethylenation and subsequent methylation to N-(4-hydroxy-3-methoxybenzyl)piperazine followed by partial glucuronidation or sulfation. Additionally, degradation of the piperazine moiety to N-(3,4-methylenedioxybenzyl)ethylenediamine and 3,4-methylenedioxybenzylamine and N-dealkylation to piperazine were observed. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS after acid hydrolysis, liquid/liquid extraction and microwave-assisted acetylation allowed the detection of MDBP and its above-mentioned metabolites in rat urine after single administration of a dose calculated from the doses commonly taken by Drug users. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of MDBP by analysis of human urine. Copyright © 2004 John Wiley & Sons, Ltd.

  • in vivo metabolism of the new Designer Drug 1 4 methoxyphenyl piperazine meopp in rat and identification of the human cytochrome p450 enzymes responsible for the major metabolic step
    Xenobiotica, 2004
    Co-Authors: Roland F Staack, Denis S Theobald, Liane D Paul, Dietmar Springer, Thomas Kraemer, Hans H Maurer
    Abstract:

    1. The in vivo metabolism of 1-(4-methoxyphenyl)piperazine (MeOPP), a novel Designer Drug, was studied in male Wistar rats.2. MeOPP was mainly O-demethylated to 1-(4-hydroxyphenyl)piperazine (4-HO-PP) in addition to degradation of the piperazine moiety.3. O-demethylation, the major metabolic step, was studied with cDNA-expressed human hepatic cytochrome P450 (CYP) enzymes in pooled human liver microsomes (pHLM) and in single donor human liver microsomes with CYP2D6 poor metabolizer genotype (PM HLM).4. CYP2D6 catalysed O-demethylation with apparent Km and Vmax values of 48.34 ± 14.48 µM and 5.44 ± 0.47 pmol min−1 pmol−1 CYP, respectively. pHLM catalysed the monitored reaction with an apparent Km = 204.80 ± 51.81 µM and Vmax = 127.50 ± 13.25 pmol min−1 mg−1 protein.5. The CYP2D6-specific chemical inhibitor quinidine (1 and 3 µM) significantly inhibited 4-HO-PP formation by 71.9 ± 4.8% and by 98.5% ± 0.5%, respectively, in incubation mixtures with pHLM and 200 µM MeOPP.6. O-demethylation was significantly l...

  • cytochrome p450 dependent metabolism of the new Designer Drug 1 3 trifluoromethylphenyl piperazine tfmpp in vivo studies in wistar and dark agouti rats as well as in vitro studies in human liver microsomes
    Biochemical Pharmacology, 2004
    Co-Authors: Roland F Staack, Liane D Paul, Dietmar Springer, Thomas Kraemer, Hans H Maurer
    Abstract:

    1-(3-Trifluoromethylphenyl)piperazine (TFMPP) is a Designer Drug with serotonergic properties. Previous studies with male Wistar rats (WI) had shown, that TFMPP was metabolized mainly by aromatic hydroxylation. In the current study, it was examined whether this reaction may be catalyzed by cytochrome P450 (CYP)2D6 by comparing TFMPP vs. hydroxy TFMPP ratios in urine from female Dark Agouti rats, a model of the human CYP2D6 poor metabolizer phenotype (PM), male Dark Agouti rats, an intermediate model, and WI, a model of the human CYP2D6 extensive metabolizer phenotype. Furthermore, the human hepatic CYPs involved in TFMPP hydroxylation were identified using cDNA-expressed CYPs and human liver microsomes. Finally, TFMPP plasma levels in the above mentioned rats were compared. The urine studies suggested that TFMPP hydroxylation might be catalyzed by CYP2D6 in humans. Studies using human CYPs showed that CYP1A2, CYP2D6 and CYP3A4 catalyzed TFMPP hydroxylation, with CYP2D6 being the most important enzyme accounting for about 81% of the net intrinsic clearance, calculated using the relative activity factor approach. The hydroxylation was significantly inhibited by quinidine (77%) and metabolite formation in poor metabolizer genotype human liver microsomes was significantly lower (63%) compared to pooled human liver microsomes. Analysis of the plasma samples showed that female Dark Agouti rats exhibited significantly higher TFMPP plasma levels compared to those of male Dark Agouti rats and WI. Furthermore, pretreatment of WI with the CYP2D inhibitor quinine resulted in significantly higher TFMPP plasma levels. In conclusion, the presented data give hints for possible differences in pharmacokinetics in human PM and human CYP2D6 extensive metabolizer phenotype subjects relevant for risk assessment.

Giselher Fritschi - One of the best experts on this subject based on the ideXlab platform.

  • spectroscopic characterization of 3 4 methylenedioxypyrrolidinobutyrophenone a new Designer Drug with α pyrrolidinophenone structure
    Forensic Science International, 2011
    Co-Authors: Folker Westphal, Thomas Junge, B Klein, Giselher Fritschi, Ulrich Girreser
    Abstract:

    Abstract This study presents and discusses the infrared spectroscopic, the nuclear magnetic resonance spectroscopic and mass spectrometric data of the Designer Drug 3,4 methylenedioxypyrrolidinobutyrophenone (MDPBP), a homolog of 3,4 methylenedioxypyrovalerone (MDPV). MDPBP was first seized in Germany in the year 2009. The structure elucidation of the aliphatic part of MDPBP was carried out by product ion spectrometry of the immonium ion with m/z = 112 formed after electron ionization, and by one- and two-dimensional 1 H- and 13 C NMR spectroscopy.

  • new Designer Drug α pyrrolidinovalerophenone pvp studies on its metabolism and toxicological detection in rat urine using gas chromatographic mass spectrometric techniques
    Journal of Mass Spectrometry, 2009
    Co-Authors: Christoph Sauer, Frank T. Peters, Giselher Fritschi, Markus R Meyer, Claudia Haas, Hans H Maurer
    Abstract:

    The aim of the present study was to identify the metabolites of the new Designer Drug α-pyrrolidinovalerophenone (PVP) in rat urine using GC/MS techniques. Eleven metabolites of PVP could be identified suggesting the following metabolic steps: hydroxylation of the side chain followed by dehydrogenation to the corresponding ketone; hydroxylation of the 2 �� position of the pyrrolidine ring followed by dehydrogenation to the corresponding lactam or followed by ring opening to the respective aliphatic aldehyde and further oxidation to the respective carboxylic acid; degradation of the pyrrolidine ring to the corresponding primary amine; and hydroxylation of the phenyl ring, most probably in the 4 � -position. The authors’ screening procedure for pyrrolidinophenones allowed the detection of PVP metabolites after application of a dose corresponding to a presumed user’s dose. In addition, the involvement of nine different human cytochrome P450 (CYP) isoenzymes in the side chain hydroxylation of PVP was investigated and CYP 2B6, 2C19, 2D6, and 3A4 were found to catalyze this reaction. Copyright c � 2009 John Wiley & Sons, Ltd.

  • metabolism and toxicological detection of the Designer Drug 4 iodo 2 5 dimethoxy amphetamine doi in rat urine using gas chromatography mass spectrometry
    Journal of Chromatography B, 2007
    Co-Authors: Andreas H. Ewald, Giselher Fritschi, Hans H Maurer
    Abstract:

    Studies are described on the metabolism and the toxicological analysis of the amphetamine-derived Designer Drug 4-chloro-2,5-dimethoxyamphetamine (DOC) in rat urine using gas chromatographic-mass spectrometric techniques. The metabolites identified indicated that DOC was metabolized by O-demethylation at position 2 or 5 of the phenyl ring partly followed by glucuronidation and/or sulfation. The authors’ systematic toxicological analysis procedure using full-scan gas chromatography-mass spectrometry after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation allowed the detection of an intake of a dose of DOC in rat urine that corresponds to a common Drug user’s dose. Assuming similar metabolism, the STA procedure described should be suitable as proof of an intake of DOC in human urine.

  • studies on the toxicological detection of the Designer Drug 4 bromo 2 5 dimethoxy β phenethylamine 2c b in rat urine using gas chromatography mass spectrometry
    Journal of Chromatography B, 2007
    Co-Authors: Denis S Theobald, Giselher Fritschi, Hans H Maurer
    Abstract:

    The phenethylamine-derived Designer Drug 4-bromo-2,5-dimethoxy--phenethylamine (2C-B) is known to be extensively metabolized in various species including humans. In rat urine, 2C-B was found to be excreted mainly via its metabolites. In the current study, the toxicological detection of these metabolites in the authors’ systematic toxicological analysis (STA) procedure was examined. The STA procedure using full-scan GC–MS allowed proving an intake of a common Drug abusers’ dose of 2C-B by detection of the O-demethyl deaminohydroxy and two isomers of the O-demethyl metabolites in rat urine. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of 2C-B in human urine.

  • Designer Drug 2 4 5 trimethoxyamphetamine tma 2 studies on its metabolism and toxicological detection in rat urine using gas chromatographic mass spectrometric techniques
    Journal of Mass Spectrometry, 2006
    Co-Authors: Andreas H. Ewald, Giselher Fritschi, Hans H Maurer
    Abstract:

    Studies are described on the metabolism and the toxicological detection of the amphetamine-derived Designer Drug 2,4,5-trimethoxyamphetamine (TMA-2) in rat urine using gas chromatographic/mass spectrometric (GC/MS) techniques. The identified metabolites indicated that TMA-2 was metabolized by oxidative deamination to the corresponding ketone followed by reduction to the corresponding alcohol, O-demethylation followed by oxidative deamination, and finally O,O-bis-demethylation. All metabolites carrying hydroxy groups were found to be partly excreted in urine as glucuronides and/or sulfates. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS after acid hydrolysis, liquid-liquid extraction, and microwave-assisted acetylation allowed the detection, in rat urine, of an intake of TMA-2 that corresponds to a common Drug users' dose. Assuming similar metabolism, the described STA procedure in human urine should be suitable as proof of an intake of TMA-2. Copyright © 2006 John Wiley & Sons, Ltd.

Yukihiro Goda - One of the best experts on this subject based on the ideXlab platform.

  • URB-754: A new class of Designer Drug and 12 synthetic cannabinoids detected in illegal products
    Forensic Science International, 2013
    Co-Authors: Nahoko Uchiyama, Maiko Kawamura, Ruri Kikura-hanajiri, Yukihiro Goda
    Abstract:

    Abstract URB-754 (6-methyl-2-[(4-methylphenyl)amino]-1-benzoxazin-4-one) was identified as a new type of Designer Drug in illegal products. Though many of the synthetic cannabinoids detected in illegal products are known to have affinities for cannabinoid CB 1 /CB 2 receptors, URB-754 was reported to inhibit an endocannabinoid deactivating enzyme. Furthermore, an unknown compound ( N ,5-dimethyl- N -(1-oxo-1-( p -tolyl)butan-2-yl)-2-( N ′-( p -tolyl)ureido)benzamide), which is deduced to be the product of a reaction between URB-754 and a cathinone derivative 4-methylbuphedrone (4-Me-MABP), was identified along with URB-754 and 4-Me-MABP in the same product. It is of interest that the product of a reaction between two different types of Designer Drugs, namely, a cannabinoid-related Designer Drug and a cathinone-type Designer Drug, was found in one illegal product. In addition, 12 cannabimimetic compounds, 5-fluoropentyl-3-pyridinoylindole, JWH-307, JWH-030, UR-144, 5FUR-144 (synonym: XLR11), (4-methylnaphtyl)-JWH-022 [synonym: N -(5-fluoropentyl)-JWH-122], AM-2232, (4-methylnaphtyl)-AM-2201 (MAM-2201), N -(4-pentenyl)-JWH-122, JWH-213, (4-ethylnaphtyl)-AM-2201 (EAM-2201) and AB-001, were also detected herein as newly distributed Designer Drugs in Japan. Furthermore, a tryptamine derivative, 4-hydroxy-diethyltryptamine (4-OH-DET), was detected together with a synthetic cannabinoid, APINACA, in the same product.

  • Identification and quantitation of JWH-213, a cannabimimetic indole, as a Designer Drug in a herbal product
    Forensic Toxicology, 2013
    Co-Authors: Kazunaga Takahashi, Ruri Kikura-hanajiri, Nahoko Uchiyama, Tomohide Fukiwake, Takashi Hasegawa, Masaaki Saijou, Yuji Motoki, Yukihiro Goda
    Abstract:

    In our survey of Designer Drugs in the Japanese market, a cannabimimetic indole was identified as a new active compound in a herbal product. The structure of this compound was elucidated by liquid chromatography–photodiode array–mass spectrometry (LC–PDA–MS), gas chromatography–mass spectrometry (GC–MS), high-resolution MS, and nuclear magnetic resonance (NMR) analyses. The compound was finally identified as (4-ethyl-1-naphthalenyl)(2-methyl-1-pentyl-1 H -indol-3-yl)methanone (JWH-213), an indole-based cannabinoid receptor ligand. To our knowledge, this is the first finding of JWH-213 as a Designer Drug in a herbal product. The quantitative LC–PDA analysis showed that the JWH-213 content in the product was 252 mg/pack.

  • Identification of a Novel Cannabimimetic Phenylacetylindole, Cannabipiperidiethanone, as a Designer Drug in a Herbal Product and Its Affinity for Cannabinoid CB1 and CB2 Receptors
    Chemical & Pharmaceutical Bulletin, 2011
    Co-Authors: Nahoko Uchiyama, Ruri Kikura-hanajiri, Yukihiro Goda
    Abstract:

    A new cannabimimetic phenylacetylindole (cannabipiperidiethanone, 1) has been found as an adulterant in a herbal product which contains two other known synthetic cannabinoids, JWH-122 and JWH-081, and which is distributed illegally in Japan. The identification was based on analyses using GC-MS, LC-MS, high-resolution MS and NMR. Accurate mass spectrum measurement showed the protonated molecular ion peak of 1 at m/z 377.2233 [M+H]+ and the molecular formula of 1 was C24H29N2O2. Both mass and NMR spectrometric data revealed that 1 was 2-(2-methoxyphenyl)-1-{1-[(1-methylpiperidin-2-yl)methyl]-1H-indol-3-yl}ethanone. Compound 1 has a mixed structure of known cannabimimetic compounds: JWH-250 and AM-2233. Namely, the moiety of phenylacetyl indole and N-methylpiperidin-2-yl-methyl correspond to the structure of JWH-250 and AM-2233, respectively. However, no synthetic, chemical or biological information about 1 has been reported. A binding assay of compound 1 to cannabinoid receptors revealed that 1 has affinity for the CB1 and CB2 (IC50=591, 968 nM, respectively) receptors, and shows 2.3- and 9.4-fold lower affinities than those of JWH-250. This is the first report to identify cannabimimetic compound (1) as a Designer Drug and to show its binding affinity to cannabinoid receptors.

  • determination of a new Designer Drug n hydroxy 3 4 methylenedioxymethamphetamine and its metabolites in rats using ultra performance liquid chromatography tandem mass spectrometry
    Forensic Science International, 2010
    Co-Authors: Ruri Kikurahanajiri, Maiko Kawamura, Atsuko Miyajima, Momoko Sunouchi, Yukihiro Goda
    Abstract:

    Abstract An N -hydroxy analogue of 3,4-methylendioxymethamphetamine (MDMA), N -hydroxy MDMA ( N -OH MDMA), has recently been distributed as a new Designer Drug in some Drug markets. Very little data is available to the metabolic and pharmacological properties of N -OH MDMA, although it has been reported that the N -demethyl analogue, N -hydroxy-3,4-methylenedioxyamphetamine ( N -OH MDA), is mainly metabolized to MDA in rats. In this study, an analytical method for the determination of N -OH MDMA and its metabolites in biological samples was developed, and the metabolic properties of N -OH MDMA in rats were investigated. After the i.p. administration of N -OH MDMA to pigmented hairy rats (5 mg/kg/day, 10 days), N -OH MDMA and its N -dehydroxy and N -demethyl metabolites (MDMA, N -OH MDA and MDA) in rat plasma, urine and hair samples were determined by ultra-performance LC (UPLC)–MS/MS. The hair sample was extracted by 1-h sonication and overnight soaking in 5 M hydrochloric acid–methanol (1:20). The plasma, urine, and hair extract samples were purified using a solid-phase extraction procedure. N -OH MDMA in the samples could be precisely analyzed by avoiding an alkaline environment. The parent compound very rapidly disappeared from the rat plasma ( N -OH MDMA was excreted in the rat urine as MDMA and MDA in 72 h. In the rat hair samples collected 4 weeks after the first administration, N -OH MDMA (0.03 ng/mg) and N -OH MDA (0.13 ng/mg) were clearly detected as well as MDMA (149 ng/mg) and MDA (52 ng/mg). This analytical method will be useful for the analysis of N -OH MDMA and its metabolites in biological samples.

  • identification of a cannabinoid analog as a new type of Designer Drug in a herbal product
    Chemical & Pharmaceutical Bulletin, 2009
    Co-Authors: Nahoko Uchiyama, Ruri Kikurahanajiri, Nobuo Kawahara, Yuji Haishima, Yukihiro Goda
    Abstract:

    A new type of Designer Drug, a cannabinoid analog (1), was found in a herbal product distributed on the illegal Drug market in Japan in expectation of its narcotic effect. The structure of 1 was identified by LC-MS, GC-MS, high-resolution MS, and NMR analyses. Compound 1 showed a molecular weight of 332, and accurate mass measurement exhibited its elemental composition to be C22H36O2. Together, the mass and NMR spectrometric data revealed that 1 was (1RS,3SR)-3-[4-(1,1-dimethyloctyl)-2-hydroxyphenyl]cyclohexan-1-ol, which was first synthesized in 1979 by a group at Pfizer Inc. and reported as a potent cannabinoid analog possessing cannabinoid receptor binding activity and analgesic activity in the 1990s. This is the first report to identify a cannabinoid analog in an illegal Drug.

Frank T. Peters - One of the best experts on this subject based on the ideXlab platform.

  • acute poisoning involving the pyrrolidinophenone type Designer Drug 4 methyl alpha pyrrolidinohexanophenone mphp
    Forensic Science International, 2011
    Co-Authors: Christoph Sauer, Kerstin Hoffmann, Ulrich Schimmel, Frank T. Peters
    Abstract:

    Abstract Introduction The pyrrolidinophenone-type Designer Drug 4′-methyl-alpha-pyrrolidinohexanophenone (MPHP) is presumed to be a potent psychostimulant as the structurally related Drug pyrovalerone. This is the first report of an acute poisoning involving MPHP. Case history A 27 year old man was admitted to hospital in an agitated state and with fractures of both feet after jumping from a window. He had reportedly snorted a powder supposed to be cocaine on the previous day and taken amyl nitrite several days before. He presented with pronounced rhabdomyolysis and had to be treated by repeated hemodialysis. Elevated liver parameters indicated toxic liver damage. Toxicological analysis The presumed cocaine powder was analyzed by gas chromatography–mass spectrometry (GC–MS) and high-performance liquid chromatography with diode array detection. The liquid and the urine samples were analyzed by headspace gas chromatography with flame ionization detection. Urine was submitted to enzymatic conjugate cleavage and further worked up by liquid–liquid extraction and acetylation or by mixed-mode solid-phase extraction (SPE) and trimethylsilylation. Serum was worked up by mixed-mode SPE. All extracts were analyzed by fullscan GC–MS. Results The powder and liquid were identified as MPHP and amyl nitrite, respectively. In the serum sample, MPHP was found in a concentration of approximately 100 ng/ml, while its 4′-carboxy metabolite was detected in urine. Amyl nitrite was not found in urine. Conclusion The use of MPHP instead of cocaine is in line with its presumed stimulant properties. The presented data indicate that it can lead to serious poisoning with toxic liver damage and rhabdomyolysis.

  • new Designer Drug α pyrrolidinovalerophenone pvp studies on its metabolism and toxicological detection in rat urine using gas chromatographic mass spectrometric techniques
    Journal of Mass Spectrometry, 2009
    Co-Authors: Christoph Sauer, Frank T. Peters, Giselher Fritschi, Markus R Meyer, Claudia Haas, Hans H Maurer
    Abstract:

    The aim of the present study was to identify the metabolites of the new Designer Drug α-pyrrolidinovalerophenone (PVP) in rat urine using GC/MS techniques. Eleven metabolites of PVP could be identified suggesting the following metabolic steps: hydroxylation of the side chain followed by dehydrogenation to the corresponding ketone; hydroxylation of the 2 �� position of the pyrrolidine ring followed by dehydrogenation to the corresponding lactam or followed by ring opening to the respective aliphatic aldehyde and further oxidation to the respective carboxylic acid; degradation of the pyrrolidine ring to the corresponding primary amine; and hydroxylation of the phenyl ring, most probably in the 4 � -position. The authors’ screening procedure for pyrrolidinophenones allowed the detection of PVP metabolites after application of a dose corresponding to a presumed user’s dose. In addition, the involvement of nine different human cytochrome P450 (CYP) isoenzymes in the side chain hydroxylation of PVP was investigated and CYP 2B6, 2C19, 2D6, and 3A4 were found to catalyze this reaction. Copyright c � 2009 John Wiley & Sons, Ltd.

  • biotechnological synthesis of the Designer Drug metabolite 4 hydroxymethyl α pyrrolidinohexanophenone in fission yeast heterologously expressing human cytochrome p450 2d6 a versatile alternative to multistep chemical synthesis
    Journal of Analytical Toxicology, 2009
    Co-Authors: Frank T. Peters, Josef Zapp, Matthias Bureik, Calinaurel Dragan, Anne Kauffels, Andrea E Schwaninger, Hans H Maurer
    Abstract:

    : 1-(4-Methylphenyl)-2-pyrrolidin-1-ylhexan-1-one (4'-methyl-alpha-pyrrolidinohexanophenone, MPHP) is a new Designer Drug that appeared on the illicit Drug market. It is mainly metabolized to 4'-hydroxymethyl-alpha-pyrrolidinohexanophenone (HO-MPHP) followed by oxidation to the respective carboxylic acid. For studies on the quantitative involvement of human cytochrome P450 (CYP) isoenzymes in the initial hydroxylation, a reference standard of HO-MPHP was needed. Therefore, the aim of this study was to synthesize this metabolite using a biotechnological approach. MPHP.HNO(3) (250 micromol) was incubated with 1 L culture of the fission yeast (Schizosaccharomyces pombe) strain CAD64 heterologously co-expressing human CYP reductase and CYP2D6. After centrifugation, the product was isolated from the incubation supernatants by solid-phase extraction. Further product cleanup was achieved by semi-preparative high-performance liquid chromatography (HPLC). After extraction of HO-MPHP from the respective eluent fractions, it was precipitated as its hydrochloric salt. The final product HO-MPHP.HCl was obtained in a yield of 138 micromol (43 mg, 55%). Its identity was confirmed by full scan gas chromatography-mass spectrometry (after trimethylsilylation), (1)H-NMR, and (13)C-NMR. The product purity as estimated from HPLC-ultraviolet analysis was greater than 99%. The described biotechnological approach proved to be a versatile alternative to the chemical synthesis of HO-MPHP.

  • biotechnological synthesis of Drug metabolites using human cytochrome p450 2d6 heterologously expressed in fission yeast exemplified for the Designer Drug metabolite 4 hydroxymethyl α pyrrolidinobutyrophenone
    Biochemical Pharmacology, 2007
    Co-Authors: Frank T. Peters, Markus R Meyer, Calina Dragan, Desiree R Wilde, Josef Zapp, Matthias Bureik, Hans H Maurer
    Abstract:

    Abstract The aim of this study was evaluating the principle feasibility of biotechnological synthesis of Drug metabolites using heterologously expressed human cytochrome P450 (CYP) enzymes. Human CYP2D6 expressed in fission yeast (Schizosaccharomyces pombe) strain CAD58 was used as model enzyme and the Designer Drug 4′-methyl-α-pyrrolidinobutyrophenone (MPBP) as model Drug. For synthesis of 4′-hydroxmethyl-α-pyrrolidinobutyrophenone (HO-MPBP), 250 μmol of MPBP·HNO3 were incubated with one litre of CAD58 culture (108 cells/mL, pH 9, 48 h, 30 °C). HO-MPBP was isolated by liquid–liquid extraction and precipitated as its hydrochloride salt. Identity and purity of the product were tested by HPLC with ultraviolet (UV) detection, GC-MS, and 1H-NMR. CAD58 was further characterized regarding the influence of incubation pH (5–10), cell density (107–108 cells/mL), and incubation time (0–120 h) on metabolite formation using the substrates dextromethorphan and MPBP. The preparative experiment yielded 40 mg (141 μmol) of HO-MPBP·HCl with a purity of >98%. In the characterization experiments, the metabolite formation rate peaked at pH 8. A linear relationship was observed between cell density and metabolite formation (R2 > 0.996). The rate of metabolite formation was slower in the earlier stages of incubation but then increased. For HO-MPBP, it became constant in the time interval of 2.5–34 h (R2 > 998).

  • Studies on the metabolism and toxicological detection of the Designer Drug 4-methylthioamphetamine (4-MTA) in human urine using gas chromatography-mass spectrometry.
    Journal of Chromatography B, 2005
    Co-Authors: Andreas H. Ewald, Frank T. Peters, Magdalene Weise, Hans H Maurer
    Abstract:

    Abstract 4-Methylthioamphetamine (4-MTA) is a scheduled Designer Drug that has appeared on the illicit Drug market and led to several non-fatal or even fatal poisonings. Only few data are available on its metabolism. The first aim of this study was to identify the 4-MTA metabolites in human urine and then to study whether the authors’ STA procedure is suitable for screening for and identification of 4-MTA and/or its metabolites in urine. After enzymatic cleavage of conjugates, solid-phase extraction (SPE) and acetylation the following metabolites could be identified by full-scan gas chromatography–mass spectrometry (GC–MS): deamino-oxo 4-MTA, deamino-hydroxy 4-MTA, ring hydroxy and β-hydroxy 4-MTA. 4-MTA sulfoxide could be identified as possible artifact. In urine samples after enzymatic hydrolysis, acidic extraction, and methylation, 4-methylthiobenzoic acid could be identified. The authors’ systematical toxicological analysis (STA) procedure using full-scan GC–MS after acid hydrolysis, liquid–liquid extraction (LLE) and acetylation allowed detection of 4-MTA as target analyte plus all the above-mentioned metabolites with the exception of 4-methylthiobenzoic acid. The extraction efficiency of 4-MTA was approximately 70% and the limit of detection (LOD) was 30 ng/ml ( S / N 3).