• P-ISSN2233-4203
  • E-ISSN2093-8950

Article Detail

Home > Article Detail
  • P-ISSN 2233-4203
  • E-ISSN 2093-8950

Identification of ML106 Phase 1 Metabolites in Human Liver Microsomes Using High-Resolution Quadrupole-Orbitrap Mass Spectrometry

Mass Spectrometry Letters, (P)2233-4203; (E)2093-8950
2016, v.7 no.3, pp.69-73
https://doi.org/10.5478/MSL.2016.7.3.69
Jo Jun Hyeon (Kyungpook National University)
Nam WoongShik (Kyungpook National University)
Kim Sunjoo (Kyungpook National University)
Lee Doohyun (Kyungpook National University)
Min Kyung Hoon (Chung-Ang University)
Lee Taeho (Kyungpook National University)
Lee Sangkyu (Kyungpook National University)
  • Downloaded
  • Viewed

Abstract

High-resolution quadrupole-Orbitrap mass spectrometry (HRMS), with high-resolution (> 10,000 at full-width at half-maximum) and accurate mass (< 5 ppm deviation) capabilities, plays an important role in the structural elucidation of drug metabolites in the pharmaceutical industry. ML106, a derivative of imidazobenzimidazole, decreased melanin content and tyrosinase activity in a dose-dependent manner. Here, we investigated the phase 1 metabolic pathway of ML106 using HRMS in human liver microsomes (HLMs) and recombinant cDNA-expressed cytochrome P450 (CYP). After the incubation of ML106 with pooled HLMs and recombinant cDNA-expressed CYP in the presence of NADPH, five phase 1 metabolites, including three mono-hydroxylated metabolites (M1-3) and two di-hydroxylated metabolites (M4 and M5), were investigated. The metabolite structures were postulated by the elucidation of protonated mass spectra using HRMS. The CYP isoforms related to the hydroxylation of ML106 were studied after incubation with recombinant cDNA-expressed CYP. Here, we identified the phase 1 metabolic pathway of ML106 induced by CYP in HLMs.

keywords
ML106 high-resolution quadrupole-Orbitrap mass spectrometry cytochrome P450 phase 1 metabolism


Reference

1

Wilson, I. D.. (2016). . Transl. Res, , -.

2

Sanoh, S.. (2015). . Yakugaku Zasshi, 135, 1273-.

3

Grund, B.. (2016). . J. Pharmaceut. Biomed, 124, 48-.

4

Meyer, M. R.. (2012). . Anal. Bioanal. Chem, 403, 1221-.

5

Wagner, D. S.. (2013). . Bioanalysis, 5, 463-.

6

Zhu, M.. (2011). . J. Biol. Chem, 286, 25419-.

7

Kim, Y. S.. (2014). . Pharmazie, 69, 353-.

Submission Date
2016-08-03
Revised Date
2016-09-22
Accepted Date
2016-09-22
상단으로 이동

Mass Spectrometry Letters