ORCID Profile
0000-0002-7495-7433
Current Organisation
Institute of Forensic Medicine Münster, University of Münster
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Publisher: Springer Science and Business Media LLC
Date: 25-07-2020
DOI: 10.1007/S00414-020-02380-3
Abstract: While the impact of genetic polymorphisms on the metabolism of various pharmaceuticals is well known, more data are needed to better understand the specific influence of pharmacogenetics on the metabolism of delta 9-tetrahydocannabinol (Δ9-THC). Therefore, the aim of the study was to analyze the potential impact of variations in genes coding for phase I enzymes of the Δ9-THC metabolism. First, a multiplex assay for genotyping different variants of genes coding for phase I enzymes was developed and applied to 66 Δ9-THC-positive blood s les obtained in cases of driving under the influence of drugs (DUID). Genetic and demographic data as well as plasma concentrations of Δ9-THC, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC), and 11-nor-9-carboxy-Δ9-THC (Δ9-THC-COOH) were combined and statistically investigated. For cytochrome P450 2C19 (CYP2C19) variants, no differences in analyzed cannabinoid concentrations were found. There were also no differences in the concentrations of Δ9-THC and 11-OH-Δ9-THC for the different allelic CPY2C9 status. We recognized significantly lower Δ9-THC-COOH concentrations for CYP2C9*3 ( p = 0.001) and a trend of lower Δ9-THC-COOH concentrations for CYP2C9*2 which did not reach statistical significance ( p = 0.068). In addition, this study showed significantly higher values in the ratio of Δ9-THC/Δ9-THC-COOH for the carriers of the CYP2C9 variants CYP2C9*2 and CYP2C9*3 compared with the carriers of the corresponding wild-type alleles. Therefore, an impact of variations of the CYP2C9 gene on the interpretation of cannabinoid plasma concentrations in DUID cases should be considered.
Publisher: Springer Science and Business Media LLC
Date: 03-12-2011
DOI: 10.1007/S00414-011-0652-8
Abstract: A liquid chromatography-electrospray ionization/tandem mass spectrometry method for the quantitation of psilocin in plasma is presented. S le workup was performed with mixed-mode solid-phase extraction using ascorbic acid and nitrogen for drying to protect the unstable analyte. Calibration curves were linear from 2 to 100 ng/mL, and no selectivity problems occurred. The limit of detection was 0.1 ng/mL, and the limit of quantitation was 0.34 ng/mL. Recovery was >86% and matrix effects were <110%. Both were reproducible. Interday and intraday precisions at different concentrations were 1.5-4.3% relative standard deviation, bias within ±9%. Processed s les were stable in the autos ler for at least 26 h. Furthermore, the stability of psilocin in blood stored at different temperatures over various periods of time was investigated. S les stored at room temperature showed a continuous decrease of analyte leading to a loss of about 90% after 1 week. Storage in the fridge improved s le stability significantly. Freezing of blood s les led to a not reproducible loss of psilocin.
Publisher: Springer Science and Business Media LLC
Date: 17-02-2010
DOI: 10.1007/S00414-010-0422-Z
Abstract: Meta-chlorophenylpiperazine, one of the synthetic piperazine-derived designer drugs, is to date controlled as an illicit substance in five European member states. Depending on the position of the chlorine atom, different positional isomers of CPP (ortho-, meta- and para-) are possible. Therefore, there is a need to develop an analytical method for the separation and identification of the three 1-chlorophenylpiperazines in tablets containing CPP. In this work, the position isomers o-, m- and p-CPP were separated by liquid chromatography (HPLC) on a reversed-phase chiral column. Different mobile phase compositions and pH ranges were systematically studied to find optimum chromatographic conditions. Best results were achieved with isocratic mobile phase of triethyl amine buffer and methanol (V/V = 70/30) at pH 9 with a flow rate of 0.8 ml/min. The method was validated in terms of selectivity, linearity, limit of detection and quantification and precision. At last, the developed method was successfully applied on seized ecstasy tablets.
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.FORSCIINT.2014.01.006
Abstract: A two-step synthesis of psilocin glucuronide (PCG), the main metabolite of psilocin, with methyl 2,3,4-tri-O-isobutyryl-1-O-trichloroacetimidoyl-α-d-glucopyranuronate is reported. With the synthesized PCG, hydrolysis conditions in serum and urine were optimized. Escherichia coli proved to be a better enzyme source for β-glucuronidase than Helix pomatia. It was essential to add ascorbic acid to serum s les to protect psilocin during incubation. Furthermore the stability of PCG and psilocin was compared as stability data are the basis for forensic interpretation of measurements. PCG showed a greater long-term stability after six months in deep frozen serum and urine s les than psilocin. The short-term stability of PCG for one week in whole blood at room temperature and in deep frozen s les was also better than that of psilocin. Therefore, PCG can be considered to be more stable than the labile psilocin and should always be included if psilocin is analyzed in s les.
Publisher: Springer Science and Business Media LLC
Date: 03-02-2017
Publisher: Springer Science and Business Media LLC
Date: 17-08-2020
DOI: 10.1007/S00414-020-02387-W
Abstract: (−)-Δ-9-tetrahydrocannabinol ((−)-Δ-9-THC) is the main psychoactive constituent in cannabis. During phase I metabolism, it is metabolized to (−)-11-hydroxy-Δ-9-tetrahydrocannabinol ((−)-11-OH-Δ-9-THC), which is psychoactive, and to (−)-11-nor-9-carboxy-Δ-9-tetrahydrocannabinol ((−)-Δ-9-THC-COOH), which is psychoinactive. It is glucuronidated during phase II metabolism. The biotransformation of (−)-Δ-9-tetrahydrocannabinol-glucuronide ((−)-Δ-9-THC-Glc) and (−)-11-nor-9-carboxy-Δ-9-tetrahydrocannabinol-glucuronide ((−)-Δ-9-THC-COOH-Glc) is well understood, which is mainly due to the availability of commercial reference standards. Since such a standardized reference is not yet available for (−)-11-hydroxy-Δ-9-tetrahydrocannabinol-glucuronide ((−)-11-OH-Δ-9-THC-Glc), its biotransformation is harder to study and the nature of the glucuronide bonding—alcoholic and/or phenolic—remains unclear. Consequently, the aim of this study was to investigate the biotransformation of (−)-11-OH-Δ-9-THC-Glc in vitro as well as in vivo and to identify the glucuronide by chemically synthesis of a reference standard. For in vitro analysis, pooled human S9 liver fraction was incubated with (−)-Δ-9-THC. Resulting metabolites were detected by high-performance liquid chromatography system coupled to a high-resolution mass spectrometer (HPLC-HRMS) with heated electrospray ionization (HESI) in positive and negative full scan mode. Five different chromatographic peaks of OH-Δ-9-THC-Glc have been detected in HESI positive and negative mode, respectively. The experiment set up according to Wen et al. indicates the two main metabolites being an alcoholic and a phenolic glucuronide metabolite. In vivo analysis of urine ( n = 10) and serum ( n = 10) s les from cannabis users confirmed these two main metabolites. Thus, OH-Δ-9-THC is glucuronidated at either the phenolic or the alcoholic hydroxy group. A double glucuronidation was not observed. The alcoholic (−)-11-OH-Δ-9-THC-Glc was successfully chemically synthesized and identified the main alcoholic glucuronide in vitro and in vivo. (−)-11-OH-Δ-9-THC-Glc is the first reference standard for direct identification and quantification. This enables future research to answer the question whether phenolic or alcoholic glucuronidation forms the predominant way of metabolism.
Publisher: Georg Thieme Verlag
Date: 2019
Publisher: Oxford University Press (OUP)
Date: 23-12-2015
DOI: 10.1093/JAT/BKU141
Abstract: A method for the simultaneous extraction of the hallucinogens psilocin, bufotenine, lysergic acid diethylamide (LSD) as well as iso-LSD, nor-LSD and O-H-LSD from hair with hydrochloride acid and methanol is presented. Clean-up of the hair extracts is performed with solid phase extraction using a mixed-mode cation exchanger. Extracts are measured with liquid chromatography coupled with electrospray tandem mass spectrometry. The method was successfully validated according to the guidelines of the 'Society of Toxicological and Forensic Chemistry' (GTFCh). To obtain reference material hair was soaked in a solution of the analytes in dimethyl sulfoxide/methanol to allow incorporation into the hair. These fortified hair s les were used for method development and can be employed as quality controls.
Publisher: Springer Science and Business Media LLC
Date: 05-10-2017
DOI: 10.1007/S00414-017-1692-5
Abstract: The ∆9-tetrahydrocannabinol (THC) metabolites 8β-hydroxy-THC and 8β,11-dihydroxy-THC are mentioned in the literature as potential blood markers of recent cannabis use. However, the formation of these metabolites in in vivo detectable concentrations has been described controversially. Therefore, the aim of this study was to verify the in vivo metabolism of 8β-hydroxy-THC and 8β,11-dihydroxy-THC in order to evaluate their potential as blood markers of recent cannabis use. First, we developed and validated a solid-phase-extraction method coupled with gas chromatography-mass spectrometry in order to enable the selective and very sensitive determination of 8β-hydroxy-THC and 8β,11-dihydroxy-THC. The application of this method in the analysis of 70 authentic plasma s les of cannabis users revealed positive results for both analytes. We detected 8β-hydroxy-THC in three and 8β,11-dihydroxy-THC in 37 out of the 70 analyzed s les. For 8β-hydroxy-THC, all of the three positive results were below the limit of quantification (LOQ 0.3 ng/mL) but above the limit of detection (LOD 0.2 ng/mL). For 8β,11-dihydroxy-THC, only two positive results were below the LOQ (0.4 ng/mL) but above the LOD (0.3 ng/mL) the remaining 35 were quantified. Hence, we were able to prove the in vivo metabolism from THC to both 8β-hydroxy-THC and 8β,11-dihydroxy-THC in detectable concentrations. The quantitative comparison of 8β-hydroxy-THC and 8β,11-dihydroxy-THC with the main cannabinoids THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC revealed no further informative value for 8β-hydroxy-THC regarding the last time of cannabis consumption. However, the detectability from 8β,11-dihydroxy-THC compared to 11-hydroxy-THC suggests a shorter detection time for 8β,11-dihydroxy-THC and thereby a promising application of this metabolite as a blood marker of recent cannabis use.
Publisher: Springer Science and Business Media LLC
Date: 06-09-2018
DOI: 10.1007/S00414-018-1919-0
Abstract: We present a novel multiplex assay for the simultaneous detection of 12 polymorphisms within the UGT1A9 sequence, which codes for enzymes involved in phase II biotransformation. The assay combines a multiplexed lification step with single-base extension sequencing. The method described here is fast, cost-effective, and easy-to-use, combining the relevant features of screening methods for research and diagnostics in pharmacogenetics. To validate the assay, we tested reproducibility and sensitivity and analysed allele frequencies of 110 Caucasian in iduals. Furthermore, we describe combining genetic information of in iduals consuming Cannabis sativa products with respective plasma concentrations of a metabolite.
Publisher: Springer Science and Business Media LLC
Date: 12-04-2016
DOI: 10.1007/S00414-016-1368-6
Abstract: The aim of this work was to develop and validate a solid-phase extraction (SPE) method for the analysis of cannabinoids with emphasis on a very extensive and effective matrix reduction in order to ensure constant good results in selectivity and sensitivity regardless of the applied measuring technology. This was obtained by the use of an anion exchange sorbent (AXS) and the purposive ionic interaction between matrix components and this sorbent material. In a first step, the neutral cannabinoids ∆9-tetrahydrocannabinol (THC) and 11-hydroxy-∆9-tetrahydrocannabinol (11-OH-THC) were eluted, leaving 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THC-COOH) and the main interfering matrix components bound to the AXS. In a second step, exploiting differences in pH and polarity, it was possible to separate matrix components and THC-COOH, thereby yielding a clean elution of THC-COOH into the same collecting tube as THC and 11-OH-THC. Even when using a simple measuring technology like gas chromatography with single quadrupole mass spectrometry, this two-step elution allows for an obvious decrease in number and intensity of matrix interference in the chromatogram. Hence, in both plasma and serum, the AXS extracts resulted in very good selectivity. Limits of detection and limits of quantification were below 0.25 and 0.35 ng/mL for the neutral cannabinoids in both matrices, 2.0 and 3.0 ng/mL in plasma and 1.6 and 3.3 ng/mL in serum for THC-COOH. The recoveries were ≥79.8 % for all analytes. Interday and intraday imprecisions ranged from 0.8 to 6.1 % relative standard deviation, and accuracy bias ranged from -12.6 to 3.6 %.
Publisher: MDPI AG
Date: 23-06-2020
DOI: 10.3390/MD18060327
Abstract: The Antarctic sponge Dendrilla antarctica is rich in defensive terpenoids with promising antimicrobial potential. Investigation of this demosponge has resulted in the generation of a small chemical library containing diterpenoid secondary metabolites with bioactivity in an infectious disease screening c aign focused on Leishmania donovani, Plasmodium falciparum, and methicillin-resistant Staphylococcus aureus (MRSA) biofilm. In total, eleven natural products were isolated, including three new compounds designated dendrillins B–D (10–12). Chemical modification of abundant natural products led to three semisynthetic derivatives (13–15), which were also screened. Several compounds showed potency against the leishmaniasis parasite, with the natural products tetrahydroaplysulphurin-1 (4) and dendrillin B (10), as well as the semisynthetic triol 15, displaying single-digit micromolar activity and low mammalian cytotoxicity. Triol 15 displayed the best profile against the liver-stage malaria parasites, while membranolide (5) and dendrillin C (11) were strong hits against MRSA biofilm cultures.
Publisher: Springer Science and Business Media LLC
Date: 27-11-2012
DOI: 10.1007/S00414-012-0796-1
Abstract: A validated method for the simultaneous determination of psilocin, bufotenine, lysergic acid diethylamide and its metabolites in serum, plasma and urine using liquid chromatography-electrospray ionization/tandem mass spectrometry was developed. During the solid-phase extraction procedure with polymeric mixed-mode cation exchange columns, the unstable analytes were protected by ascorbic acid, drying with nitrogen and exclusion of light. The limits of detection and quantitation for all analytes were low. Recovery was ≥86 % for all analytes and no significant matrix effects were observed. Interday and intraday imprecisions at different concentrations ranged from 1.1 to 8.2 % relative standard deviation, bias was within ±5.3 %. Processed s les were stable in the autos ler for at least 2 days. Furthermore, freeze/thaw and long-term stability were investigated. The method was successfully applied to authentic serum and urine s les.
Location: No location found
Location: Germany
Start Date: 2018
End Date: 2018
Funder: Deutsche Forschungsgemeinschaft
View Funded ActivityStart Date: 2016
End Date: 2016
Funder: Deutsche Forschungsgemeinschaft
View Funded Activity