Metabolic profiling of deschloro‐ N ‐ethyl‐ketamine and identification of new target metabolites in urine and hair using human liver microsomes and high‐resolution accurate mass spectrometry

2021 ◽  
Author(s):  
Islam Amine Larabi ◽  
Fanny Zerizer ◽  
Alice Ameline ◽  
Isabelle Etting ◽  
Delphine Joseph ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Metabolic Profiling ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Accurate Mass ◽  
Accurate Mass Spectrometry ◽  
High Resolution Accurate 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 Identification of ML106 Phase 1 Metabolites in Human Liver Microsomes Using High-Resolution Quadrupole-Orbitrap Mass Spectrometry

2016 ◽  
Vol 7 (3) ◽  
pp. 69-73 ◽  
Author(s):  
Jun Hyeon Jo ◽  
WoongShik Nam ◽  
Sunjoo Kim ◽  
Doohyun Lee ◽  
Kyung Hoon Min ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Resolution ◽  
Human Liver ◽  
Phase 1 ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Orbitrap Mass Spectrometry

scholarly journals Non-targeted Screening of Commercial CBD Products in the United States Reveals Common Contamination and Adulteration

2020 ◽  
Author(s):  
Ben Orsburn
Keyword(s):  
United States ◽  
Mass Spectrometry ◽  
High Resolution ◽  
The United States ◽  
Mass Spectrometry Data ◽  
Accurate Mass ◽  
Targeted Screening ◽  
Accurate Mass Spectrometry ◽  
High Concentrations ◽  
High Resolution Accurate Mass

AbstractThe production of hemp and products derived from these plants that contain zero to trace amounts of the psychoactive cannabinoid tetrahydrocannabidiol (THC) is a rapidly growing new market in the United States. The most common products today contain relatively high concentrations of the compound cannabidiol (CBD). Recent studies have investigated commercial CBD products using targeted assays and have found varying degrees of misrepresentation and contamination of these products. To expand on previous studies, we demonstrate the application of non-targeted screening by high resolution accurate mass spectrometry to more comprehensively identify potential adulterants and contaminants. We find evidence to support previous conclusions that CBD products are commonly misrepresented in terms of cannabinoid concentrations present. Specifically, we observe a wide variation in relative THC concentrations across the product tested, with some products containing 10-fold more relative signal than others. In addition, we find that several products appear to be purposely adulterated with over the counter drugs such as caffeine and melatonin. We also observe multiple small molecule contaminants that are typically linked to improper production or packaging methods in food or pharmaceutical production. Finally, we present high resolution accurate mass spectrometry data and tandem MS/MS fragments supporting the presence of trace amounts of fluorofentanyl in a single mail order CBD product. We conclude that the CBD industry would benefit from more robust testing regulations and that the cannabis testing industry, in general, would benefit from the use of non-targeted screening technologies.

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