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A high-resolution MS/MS based strategy to improve xenobiotic metabolites analysis by metabolic pathway extension searching combined with parallel reaction monitoring: Flavonoid metabolism in wound site as a case
- Source :
- Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 1162
- Publication Year :
- 2020
-
Abstract
- For the analysis of xenobiotic metabolism, metabolites are commonly qualified by high-resolution mass spectrometry such as orbitrap or time-of-flight mass spectrometers, and quantified by triple-quadrupole (QQQ) mass spectrometer based multiple reaction monitoring. While this workflow shows drawback in the difficulty for instrumental parameters transfer, and QQQ provides less specificity. In this work, we constructed a high-resolution MS/MS (HR-MS/MS) based strategy to improve the discovery and quantification of unknown xenobiotic metabolites by metabolic pathway extension (MPE) searching combined with parallel reaction monitoring (PRM). Taking the flavonoid metabolism in diabetes wound S9 incubates as a test case. Firstly, MPE approach was used to screen all potential metabolites. In this step, an m/z value library of all theoretic flavonoid metabolites were constructed based on predefined flavonoid structures through 21 common xenobiotic metabolic reactions, and this library was matched with all features extracted from raw data (MS1 scan) of flavonoid-S9 co-incubate, then the matched features were exported into target list for MS2 fragmentation for structure validation. Secondly, the metabolites were relatively quantified by PRM mode based on their characteristic product ions. As a result, 131 metabolites of 9 different kinds of flavonoids in the skin and muscle were identified. To our best knowledge, this is the first report on the metabolism of flavonoids in the skin or muscle tissue. The results also validated the proposed HR-MS/MS-based strategy provided high specificity throughout both discovery and quantitation process of unknown xenobiotic metabolites without need of instrumental parameter transfer.
- Subjects :
- Male
Clinical Biochemistry
Flavonoid
Orbitrap
Mass spectrometry
030226 pharmacology & pharmacy
01 natural sciences
Biochemistry
Analytical Chemistry
law.invention
Diabetes Mellitus, Experimental
Xenobiotics
Diabetes Complications
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
Flavonoid metabolism
0302 clinical medicine
law
Tandem Mass Spectrometry
Animals
Chromatography, High Pressure Liquid
Skin
chemistry.chemical_classification
Flavonoids
Chromatography
Chemistry
Muscles
010401 analytical chemistry
Selected reaction monitoring
Cell Biology
General Medicine
0104 chemical sciences
Rats
Metabolic pathway
Xenobiotic
Drug metabolism
Subjects
Details
- ISSN :
- 1873376X
- Volume :
- 1162
- Database :
- OpenAIRE
- Journal :
- Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
- Accession number :
- edsair.doi.dedup.....9be90a105088e00d6ecc9874362b3a83