Novel polar AhR-active chemicals detected in sediments of an industrial area using effect-directed analysis based on in vitro bioassays with full-scan high resolution mass spectrometric screening

2021 ◽  
Vol 779 ◽  
pp. 146566
Author(s):  
Jihyun Cha ◽  
Seongjin Hong ◽  
Junghyun Lee ◽  
Jiyun Gwak ◽  
Mungi Kim ◽  
...  
Keyword(s):  
High Resolution ◽  
Industrial Area ◽  
Mass Spectrometric ◽  
High Resolution Mass ◽  
Full Scan ◽  
In Vitro Bioassays ◽  
Effect Directed Analysis ◽  
Resolution Mass

scholarly journals Human Hepatocyte Metabolism of Novel Synthetic Cannabinoids MN-18 and Its 5-Fluoro Analog 5F-MN-18

2017 ◽  
Vol 63 (11) ◽  
pp. 1753-1763 ◽  
Author(s):  
Xingxing Diao ◽  
Jeremy Carlier ◽  
Mingshe Zhu ◽  
Marilyn A Huestis
Keyword(s):  
Carboxylic Acid ◽  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
Synthetic Cannabinoids ◽  
Human Hepatocytes ◽  
Binding Affinities ◽  
High Resolution Mass ◽  
Full Scan ◽  
Resolution Mass

Abstract BACKGROUND In 2014, 2 novel synthetic cannabinoids, MN-18 and its 5-fluoro analog, 5F-MN-18, were first identified in an ongoing survey of novel psychoactive substances in Japan. In vitro pharmacological assays revealed that MN-18 and 5F-MN-18 displayed high binding affinities to human CB1 and CB2 receptors, with Ki being 1.65–3.86 nmol/L. MN-18 and 5F-MN-18 were scheduled in Japan and some other countries in 2014. Despite increasing prevalence, no human metabolism data are currently available, making it challenging for forensic laboratories to confirm intake of MN-18 or 5F-MN-18. METHODS We incubated 10 μmol/L of MN-18 and 5F-MN-18 in human hepatocytes for 3 h and analyzed the samples on a TripleTOF 5600+ high-resolution mass spectrometer to identify appropriate marker metabolites. Data were acquired via full scan and information-dependent acquisition-triggered product ion scans with mass defect filter. RESULTS In total, 13 MN-18 metabolites were detected, with the top 3 abundant metabolites being 1-pentyl-1H-indazole-3-carboxylic acid, pentyl-carbonylated MN-18, and naphthalene-hydroxylated MN-18. For 5F-MN-18, 20 metabolites were observed, with the top 3 abundant metabolites being 5′-OH-MN-18, MN-18 pentanoic acid, and 1-(5-fluoropentyl)-1H-indazole-3-carboxylic acid. CONCLUSIONS We have characterized MN-18 and 5F-MN-18 metabolism with human hepatocytes and high-resolution mass spectrometry, and we recommend characteristic major metabolites for clinical and forensic laboratories to identify MN-18 and 5F-MN-18 intake and link observed adverse events to these novel synthetic cannabinoids.

scholarly journals Gas chromatographic quadrupole time-of-flight full scan high resolution mass spectrometric screening of human urine in antidoping analysis

2017 ◽  
Vol 1063 ◽  
pp. 74-83 ◽  
Author(s):  
Wadha Abushareeda ◽  
Emmanouil Lyris ◽  
Suhail Kraiem ◽  
Aisha Al Wahaibi ◽  
Sameera Alyazidi ◽  
...  
Keyword(s):  
High Resolution ◽  
Human Urine ◽  
Time Of Flight ◽  
Mass Spectrometric ◽  
High Resolution Mass ◽  
Full Scan ◽  
Antidoping Analysis ◽  
Resolution Mass

scholarly journals Nontargeted Metabolomics by High-Resolution Mass Spectrometry to Study the In Vitro Metabolism of a Dual Inverse Agonist of Estrogen-Related Receptors β and γ, DN203368

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 776
Author(s):  
Sin-Eun Kim ◽  
Seung-Bae Ji ◽  
Euihyeon Kim ◽  
Minseon Jeong ◽  
Jina Kim ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Human Liver ◽  
High Resolution Mass Spectrometry ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Rat Liver Microsomes ◽  
High Resolution Mass ◽  
Resolution Mass

DN203368 ((E)-3-[1-(4-[4-isopropylpiperazine-1-yl]phenyl) 3-methyl-2-phenylbut-1-en-1-yl] phenol) is a 4-hydroxy tamoxifen analog that is a dual inverse agonist of estrogen-related receptor β/γ (ERRβ/γ). ERRγ is an orphan nuclear receptor that plays an important role in development and homeostasis and holds potential as a novel therapeutic target in metabolic diseases such as diabetes mellitus, obesity, and cancer. ERRβ is also one of the orphan nuclear receptors critical for many biological processes, such as development. We investigated the in vitro metabolism of DN203368 by conventional and metabolomic approaches using high-resolution mass spectrometry. The compound (100 μM) was incubated with rat and human liver microsomes in the presence of NADPH. In the metabolomic approach, the m/z value and retention time information obtained from the sample and heat-inactivated control group were statistically evaluated using principal component analysis and orthogonal partial least-squares discriminant analysis. Significant features responsible for group separation were then identified using tandem mass spectra. Seven metabolites of DN203368 were identified in rat liver microsomes and the metabolic pathways include hydroxylation (M1-3), N-oxidation (M4), N-deisopropylation (M5), N,N-dealkylation (M6), and oxidation and dehydrogenation (M7). Only five metabolites (M2, M3, and M5-M7) were detected in human liver microsomes. In the conventional approach using extracted ion monitoring for values of mass increase or decrease by known metabolic reactions, only five metabolites (M1-M5) were found in rat liver microsomes, whereas three metabolites (M2, M3, and M5) were found in human liver microsomes. This study revealed that nontargeted metabolomics combined with high-resolution mass spectrometry and multivariate analysis could be a more efficient tool for drug metabolite identification than the conventional approach. These results might also be useful for understanding the pharmacokinetics and metabolism of DN203368 in animals and humans.

scholarly journals The structure of novel C35 pentacyclic terpenes from Acetobacter xylinum

1973 ◽  
Vol 135 (1) ◽  
pp. 133-143 ◽  
Author(s):  
Hans J. Förster ◽  
Klaus Biemann ◽  
W. Geoffrey Haigh ◽  
Neil H. Tattrie ◽  
J. Ross Colvin
Keyword(s):  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
Carbon Chain ◽  
Acetobacter Xylinum ◽  
Mass Spectrometric ◽  
Hydroxyl Groups ◽  
Mass Spectral Data ◽  
Mass Spectral ◽  
High Resolution Mass ◽  
Resolution Mass

A novel C35 terpene and its monounsaturated analogue were isolated from cultures of Acetobacter xylinum, together with traces of their C36 homologues. These substances were found to be hopane derivatives substituted by a five-carbon chain bearing four vicinal hydroxyl groups. For the parent hydrocarbon the term bacteriohopane is proposed. The elucidation of the structures utilized high-resolution mass spectrometry of the terpenes, degradation to C32 hydrocarbons and detailed mass-spectrometric comparison of these with C32 hydrocarbons synthesized from known pentacyclic triterpenes. High-resolution mass-spectral data of the terpenes are presented. N.m.r. data are in agreement with the proposed structures, which are further supported by the isolation from the same organism of 22-hydroxyhopane and derivative hopene(s).

Strategy and Its Implications of Protein Bioanalysis Utilizing High-Resolution Mass Spectrometric Detection of Intact Protein

2011 ◽  
Vol 83 (23) ◽  
pp. 8937-8944 ◽  
Author(s):  
Qian Ruan ◽  
Qin C. Ji ◽  
Mark E. Arnold ◽  
W. Griffith Humphreys ◽  
Mingshe Zhu
Keyword(s):  
High Resolution ◽  
Mass Spectrometric ◽  
Mass Spectrometric Detection ◽  
Intact Protein ◽  
High Resolution Mass ◽  
Resolution Mass
Sign in / Sign up

Export Citation Format

Share Document