Determination of metformin bio-distribution by LC-MS/MS in mice treated with a clinically relevant paradigm

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dc.creatorChaudhari, Kiran
dc.creatorWang, Jianmei
dc.creatorXu, Yong
dc.creatorWinters, Ali
dc.creatorWang, Linshu
dc.creatorDong, Xiaowei
dc.creatorCheng, Eric Y.
dc.creatorLiu, Ran
dc.creatorYang, Shaohua
dc.creator.orcid0000-0001-9336-2593 (Cheng, Eric Yi-Qiang)
dc.creator.orcid0000-0002-3882-0616 (Liu, Ran)
dc.creator.orcid0000-0002-0405-0887 (Yang, Shaohua)
dc.date.accessioned2022-11-28T20:48:03Z
dc.date.available2022-11-28T20:48:03Z
dc.date.issued2020-06-11
dc.description.abstractMetformin, an anti-diabetes drug, has been recently emerging as a potential "anti-aging" intervention based on its reported beneficial actions against aging in preclinical studies. Nonetheless, very few metformin studies using mice have determined metformin concentrations and many effects of metformin have been observed in preclinical studies using doses/concentrations that were not relevant to therapeutic levels in human. We developed a liquid chromatography-tandem mass spectrometry protocol for metformin measurement in plasma, liver, brain, kidney, and muscle of mice. Young adult male and female C57BL/6 mice were voluntarily treated with metformin of 4 mg/ml in drinking water which translated to the maximum dose of 2.5 g/day in humans. A clinically relevant steady-state plasma metformin concentrations were achieved at 7 and 30 days after treatment in male and female mice. Metformin concentrations were slightly higher in muscle than in plasma, while, ~3 and 6-fold higher in the liver and kidney than in plasma, respectively. Low metformin concentration was found in the brain at ~20% of the plasma level. Furthermore, gender difference in steady-state metformin bio-distribution was observed. Our study established steady-state metformin levels in plasma, liver, muscle, kidney, and brain of normoglycemic mice treated with a clinically relevant dose, providing insight into future metformin preclinical studies for potential clinical translation.
dc.description.sponsorshipThis work was partly supported by the National Institutes of Health grants R01NS088596 (SY), R01NS109583 (SY), and American Heart Association Grant 17POST33670981 (KC).
dc.identifier.citationChaudhari, K., Wang, J., Xu, Y., Winters, A., Wang, L., Dong, X., Cheng, E. Y., Liu, R., & Yang, S. H. (2020). Determination of metformin bio-distribution by LC-MS/MS in mice treated with a clinically relevant paradigm. PloS one, 15(6), e0234571. https://doi.org/10.1371/journal.pone.0234571
dc.identifier.issn1932-6203
dc.identifier.issue6
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31984
dc.identifier.volume15
dc.publisherPLOS
dc.relation.urihttps://doi.org/10.1371/journal.pone.0234571
dc.rights.holder© 2020 Chaudhari et al.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePLoS One
dc.subject.meshAnimals
dc.subject.meshBrain / metabolism
dc.subject.meshChromatography, Liquid
dc.subject.meshFemale
dc.subject.meshKidney / metabolism
dc.subject.meshLiver / metabolism
dc.subject.meshMale
dc.subject.meshMetformin / administration & dosage
dc.subject.meshMetformin / blood
dc.subject.meshMetformin / pharmacokinetics
dc.subject.meshMice
dc.subject.meshMice, Inbred C57BL
dc.subject.meshMuscles / metabolism
dc.subject.meshTandem Mass Spectrometry
dc.subject.meshTissue Distribution
dc.titleDetermination of metformin bio-distribution by LC-MS/MS in mice treated with a clinically relevant paradigm
dc.typeArticle
dc.type.materialtext

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