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MOLECULAR CHARACTERIZATION OF FOLATE RECEPTOR 1 MUTATIONS REVEAL PHENOTYPIC VARIATIONS OF CEREBRAL FOLATE TRANSPORT DEFICIENCY
No full textToxicological investigation of forensic cases related to the designer drug 3,4-methylenedioxypyrovalerone (MDPV): Detection, quantification and studies on human metabolism by GC-MS
No full text3,4-methylenedioxypyrovalerone (MDPV) is a synthetic cathinone belonging to the class of a-pyrrolidinophenones that become increasingly popular as a designer psychostimulant. Here, we report a comprehensive collection of MDPV exposure with quantitative serum level confirmation in Germany. During the years 2014-2016, we could proof consumption of MDPV in 23 cases where urine and blood samples were submitted to our laboratory by the police of Lower Saxony. Most of the samples underwent systematic toxicological analysis by gas chromatography-mass spectrometry (GC-MS), where MDPV could be detected in urine and/or serum samples. The determined concentrations of MDPV in serum showed a high variability, ranging from traces (< 10 ng/mL) up to 576 ng/mL with a mean concentration of 118 ng/mL and median of 47 ng/mL. The majority of MDPV users were men (87%) and the age ranged from 23 to 49 years (mean 35.9, median 37 years). For most of the analytically confirmed MDPV cases we could prove co-consumption of other psychotropic drugs with frequent occurrence of opiates and cannabinoids in 22% of the cases, followed by benzodiazepines and cocaine in 17%. Analysis of urine samples by GC-MS disclosed the presence of MDPV and its metabolites 2'-oxo-MDPV, demethylenyl-MDPV, demethylenyl-methyl-MDPV, demethylenyl-oxo-MDPV, demethylenyl-methyloxo- MDPV and demethylenyl-methyl-N, N-bisdealkyl-MDPV. The metabolite pattern substantiates previous suggestions for principle metabolic pathways of MDPV in humans. (C) 2017 Elsevier B.V. All rights reserved
MOLECULAR CHARACTERIZATION OF FOLATE RECEPTOR 1 MUTATIONS REVEAL PHENOTYPIC VARIATIONS OF CEREBRAL FOLATE TRANSPORT DEFICIENCY
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GC-MS analysis of the designer drug alpha-pyrrolidinovalerophenone and its metabolites in urine and blood in an acute poisoning case
No full textalpha-Pyrrolidinovalerophenone (alpha-PVP) is a synthetic cathinone belonging to the group of "second generation'' pyrrolidinophenones that becomes more and more popular as a designer psychostimulant. Here we provide toxicological analytical support for a severe poisoning with alpha-PVP. Serum and urine samples that were sent to our laboratory were subjected to a general unknown screening procedure. The procedure includes immunoassay-based screening of drugs of abuse in serum and systematic toxicological analysis of urine and serum after neutral and basic liquid-liquid extraction followed by gas chromatography-mass spectrometry (GC-MS). Whereas the immunoassay delivered negative results, analyzing the urine sample by GC-MS in full scan mode disclosed the presence of alpha-PVP and its metabolites alpha-(2 ''-oxo-pyrrolidino)valerophenone (2 ''-oxo-alpha-PVP) and 1-phenyl-2-(pyrrolidin-1-yl) pentan-1-ol (OH-alpha-PVP). In the acetylated urine sample we found additionally N,N-bis-dealkyl-PVP. In serum, alpha-PVP could be detected after solid phase extraction and a concentration of 29 ng/mL was determined. Other forensic relevant substances were not detected. The presented data can explain the psychotic symptoms and behavioural pattern of the subject after abuse of alpha-PVP, leading to a clinical condition similar to excited delirium syndrome. (C) 2015 Elsevier Ireland Ltd. All rights reserved
Systematic forensic toxicological analysis by GC‐MS in serum using automated mass spectral deconvolution and identification system
No full textNon-targeted screening of body fluids for psychoactive agents is an essential task for forensic toxicology. The challenge is the identification of xenobiotics of interest from background noise and endogenous matrix components. The aim of the present work was to evaluate the use of an Automated Mass Spectral Deconvolution and Identification System (AMDIS) for gas chromatography-mass spectrometry (GC-MS) based toxicological serum screening. One hundred fifty serum samples submitted to the authors' laboratory for systematic forensic toxicological analysis underwent GC-MS screening after neutral and basic liquid-liquid extraction. Recorded datasets were routinely evaluated both by experienced personnel and automatically using the AMDIS software combined with theMaurer/Pfleger/Weber GC-MS library MPW_2011. The results from manual and automated data evaluation were then systematically compared. AMDIS parameters for data deconvolution and substance identification had been successfully adapted to the GC-MS screening procedure in serum. The number of false positive hits could substantially be reduced without increasing the risk of overlooking relevant compounds. With AMDIS-based data evaluation, additional drugs were identified in 25 samples (17%) that had not been detected by manual data evaluation. Importantly, among these drugs, there were frequently prescribed and toxicologically relevant antidepressants and antipsychotic drugs such as citalopram, mirtazapine, quetiapine, or venlafaxine. For most of the identified drugs, their serum concentrations were in the therapeutic or subtherapeutic range. Thus, our study indicated that automated data evaluation by AMDIS provided reliable screening results. Copyright (c) 2015 John Wiley & Sons, Ltd
Systematic forensic toxicological analysis by liquid-chromatography-quadrupole-time-of-flight mass spectrometry in serum and comparison to gas chromatography-mass spectrometry
No full textSynthesis of Formacetal‐Linked Dinucleotides to Facilitate dsDNA Bending and Binding to the Homeodomain of Pax6
No full textTwo formacetal-linked dinucleotides TT and TT were synthesized as phosphoramidite building blocks for solid-phase synthesis. Incorporated in a 29-mer DNA, the oligomers P3(TT) and P3(TA) were studied with respect to the binding activity towards the Pax6 homeodomain. Substitution of the negatively charged phosphodiester by a neutral formacetal linker facilitates the bent conformation of double-stranded DNA. The duplex stability was affected more significantly by the TT formacetal modification, whereas destabilization induced by TA was less pronounced. Based on CD spectroscopy, the TA formacetal-modified oligomer P3(TA) A has mainly B-DNA topology, whereas the P3(TT) modified oligomet significantly deviated from B-form DNA. The binding affinity of the P3 oligomer towards Pax6 HD was investigated by in vitro EMSA experiments providing even a small increase in binding affinity for the P3(TA) T oligomer. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
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