Metabolite Identification of a Novel Anti-Leishmanial Agent OJT007 in Rat Liver Microsomes Using LC-MS/MS
Abstract
:1. Introduction
2. Results and Discussion
2.1. Full Mass Scan and Product Ion Scan Spectra for Matrix Free OJT007
2.2. Metabolism of OJT007 in CYP and UGT Reaction Systems
2.2.1. CYP Mediated Phase I Metabolism
Phase I Metabolites Identification by LC-MS/MS
Metabolic Stability for Oxidation Metabolites
2.2.2. UGT Mediated Glucuronidation Metabolism
Glucuronide Identification by LC-MS/MS
Glucuronide Hydrolysis by β-Glucuronidase
Conversion Factors (K) of Extinction Coefficient
Kinetics of OJT007 Glucuronidation
3. Materials and Methods
3.1. Materials
3.2. Sample Preparation
3.3. LC-MS/MS Method
3.3.1. Chromatography
3.3.2. Mass Spectrometry
3.4. UPLC Method
3.5. In Vitro Metabolic Studies—CYP Reaction System
3.6. In Vitro Metabolic Studies—UGT Reaction System
3.7. Full Mass Scan and Product Scan Spectra for Matrix Free OJT007
3.8. Identification of Phase I Metabolites
LC-MS/MS
3.9. Identification of Phase II Metabolites
3.9.1. LC-MS/MS
3.9.2. Hydrolysis by β-Glucuronidases
3.10. Determination of Molar Extinction Coefficient of OJT007 Glucuronide
3.11. Metabolic Stability Data Analysis
3.12. Glucuronidation Metabolic Kinetics
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
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Rincon Nigro, M.E.; Du, T.; Gao, S.; Kaur, M.; Xie, H.; Olaleye, O.A.; Liang, D. Metabolite Identification of a Novel Anti-Leishmanial Agent OJT007 in Rat Liver Microsomes Using LC-MS/MS. Molecules 2022, 27, 2854. https://doi.org/10.3390/molecules27092854
Rincon Nigro ME, Du T, Gao S, Kaur M, Xie H, Olaleye OA, Liang D. Metabolite Identification of a Novel Anti-Leishmanial Agent OJT007 in Rat Liver Microsomes Using LC-MS/MS. Molecules. 2022; 27(9):2854. https://doi.org/10.3390/molecules27092854
Chicago/Turabian StyleRincon Nigro, Maria Eugenia, Ting Du, Song Gao, Manvir Kaur, Huan Xie, Omonike Arike Olaleye, and Dong Liang. 2022. "Metabolite Identification of a Novel Anti-Leishmanial Agent OJT007 in Rat Liver Microsomes Using LC-MS/MS" Molecules 27, no. 9: 2854. https://doi.org/10.3390/molecules27092854