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  • 한국과학기술정보연구원(KISTI) 서울분원 대회의실(별관 3층)
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  • P-ISSN2233-4203
  • E-ISSN2093-8950
  • ESCI, SCOPUS, KCI

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  • 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 / 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
Jun Hyeon Jo (Kyungpook National University)
WoongShik Nam (Kyungpook National University)
Sunjoo Kim (Kyungpook National University)
Doohyun Lee (Kyungpook National University)
Kyung Hoon Min (Chung-Ang University)
Taeho Lee (Kyungpook National University)
Sangkyu Lee (Kyungpook National University)
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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


참고문헌

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투고일Submission Date
2016-08-03
수정일Revised Date
2016-09-22
게재확정일Accepted Date
2016-09-22
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Mass Spectrometry Letters