Citation

Manier SK, Felske C, Eckstein N, Meyer MR. Drug Test. Anal. 2019; ePub(ePub): ePub.

Affiliation

Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Center for Molecular Signaling (PZMS), 66421, Homburg, Germany.

Copyright

(Copyright © 2019, John Wiley and Sons)

DOI

10.1002/dta.2699

PMID

31667988

Abstract

The aim of this study was to characterize the in vitro and in vivo metabolism of 2-aminoindane (2,3-dihydro-1H-inden-2-amine, 2-AI), and N-methyl-2-aminoindane (N-methyl-2,3-dihydro-1H-inden-2-amine, NM-2-AI) after incubations using pooled human liver microsomes (pHLM), pooled human liver S9 fraction (pS9), as well as rat urine after oral administration. After analysis using liquid-chromatography coupled to high-resolution mass spectrometry, pHLM incubations revealed that 2-AI was left unmetabolized, while NM-2-AI formed a hydroxylamine and diastereomers of a metabolite formed after hydroxylation in beta position. Incubations using pS9 led to the formation of an acetyl conjugation in case of 2-AI and merely a hydroxylamine for NM-2-AI. Investigations on rat urine showed that 2-AI was hydroxylated also forming diasteromers as described for NM-2-AI or acetylated similar to incubations using pS9. All hydroxylated metabolites of NM-2-AI except the hydroxylamine were found in rat urine as additional sulfates. Assuming similar patterns in humans, urine screening procedures might be focused on the parent compounds but should also include their metabolites. At last, an activity screening using human recombinant N-acetyl transferase (NAT) isoforms 1 and 2 revealed that 2-AI was acetylated exclusively by NAT2 which is polymorphically expressed.

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Language: en

Keywords

LC-HRMS/MS; NPS; aminoindanes; in vitro; in vivo; metabolism