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

Kiran Chaudhari, Jianmei Wang, Yong Xu, Ali Winters, Linshu Wang, Xiaowei Dong, Eric Y. Cheng, Ran Liu, Shao Hua Yang

Research output: Contribution to journalArticle

Abstract

Metformin, 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.

Original languageEnglish
Pages (from-to)e0234571
JournalPLoS ONE
Volume15
Issue number6
DOIs
StatePublished - 1 Jan 2020

Fingerprint Dive into the research topics of 'Determination of metformin bio-distribution by LC-MS/MS in mice treated with a clinically relevant paradigm'. Together they form a unique fingerprint.

  • Cite this