Please use this identifier to cite or link to this item: doi:10.22028/D291-32435
Title: Untargeted metabolomics by high resolution mass spectrometry coupled to normal and reversed phase liquid chromatography as a tool to study the in vitro biotransformation of new psychoactive substances
Author(s): Manier, Sascha K.
Keller, Andreas
Schäper, Jan
Meyer, Markus R.
Language: English
Title: Scientific Reports
Volume: 9
Issue: 1
Publisher/Platform: SpringerNature
Year of Publication: 2019
Free key words: Biomarkers
Data processing
Metabolomics
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: In 2016, several synthetic cathinones were seized by the State Bureau of Criminal Investigation Bavaria in Germany. Due to their previous appearances in other countries their metabolism was already investigated in human urine as well as different in vitro models. These investigations were conducted using ordinary metabolism studies for drugs of abuse by using general knowledge about drug metabolism and visual comparison of mass spectra. The present study aimed to use untargeted metabolomics to support and improve those methods that highly depend on the investigators experience. Incubations were conducted using pooled human liver microsomes (pHLM) and the two cathinones 1-phenyl-2-(1-pyrrolidinyl)-1-butanone and 1-phenyl-2-(1-pyrrolidinyl)-1-heptanone. Samples were analyzed by LC-HRMS/MS using a metabolomics workflow consisting of a reversed phase or normal phase separation followed by electrospray ionization and full scan in positive or negative mode. LC-MS data was afterwards statistically evaluated using principal component analysis, t-distributed stochastic neighborhood embedding, and hierarchical clustering. Significant features were then identified using MS/MS. The workflow revealed 24 significant features after 1-phenyl-2-(1-pyrrolidinyl)-1-butanone and 39 after 1-phenyl-2-(1-pyrrolidinyl)-1-heptanone incubation, consisting of adducts, artifacts, isomers, and metabolites. The applied untargeted metabolomics strategy was able to find almost all of the metabolites that were previously described for 1-phenyl-2-(1-pyrrolidinyl)-1-butanone in literature as well as three additional metabolites. Concerning 1-phenyl-2-(1-pyrrolidinyl)-1-heptanone biotransformation in pHLM, merely four metabolites described in primary human hepatocytes and human urine were not found. This study revealed that untargeted metabolomics workflows are well suited to support biotransformation studies at least of the investigated compounds in pHLM.
DOI of the first publication: 10.1038/s41598-019-39235-w
Link to this record: urn:nbn:de:bsz:291--ds-324350
hdl:20.500.11880/29801
http://dx.doi.org/10.22028/D291-32435
ISSN: 2045-2322
Date of registration: 5-Oct-2020
Description of the related object: Supplementary information
Related object: https://static-content.springer.com/esm/art%3A10.1038%2Fs41598-019-39235-w/MediaObjects/41598_2019_39235_MOESM1_ESM.pdf
Faculty: M - Medizinische Fakultät
Department: M - Experimentelle und Klinische Pharmakologie und Toxikologie
Professorship: M - Prof. Dr. Markus Meyer
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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