Transl Clin Pharmacol.  2021 Dec;29(4):216-225. 10.12793/tcp.2021.29.e19.

A validated simple LC-MS/MS method for quantifying trimethylamine N-oxide (TMAO) using a surrogate matrix and its clinical application

Affiliations
  • 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea
  • 2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea
  • 3Clinical Trials Center, Seoul National University Bundang Hospital, Seongnam 13620, Korea

Abstract

Trimethylamine N-oxide (TMAO) is a small molecular amine oxide generated from dietary choline and carnitine through intestinal microbial metabolism. Recently, TMAO has attracted much public attention as its role in disease progression has been proven in many clinical studies. The plasma concentration of TMAO in humans was found to be positively associated with the increased risk of many diseases including cardiovascular diseases and chronic kidney diseases. To achieve accurate and sensitive quantitation of TMAO for clinical applications, we established and validated a simple quantitative method using a liquid chromatography tandem mass spectrometry (LC-MS/MS) system. We constructed an eight-point calibration curve in an artificial surrogate matrix instead of the commonly used biological matrices to avoid interference from the endogenous TMAO. The calibration curve showed excellent linearity in the range of 1 to 5,000 ng/mL, with a correlation coefficient (R2 ) higher than 0.996 in each validation batch. Moreover, both the intra-day and inter-day assays achieved satisfactory precision and accuracy results ranging from 1.65–7.15% and 96.36–111.43%, respectively. Further, this method was cross-validated using a human plasma matrix and applied to a clinical pharmacology study. Overall, these results demonstrate that the developed quantitation method is applicable in clinical research for monitoring disease progression and evaluating drug effects.

Keyword

TMAO; Biomarkers; Liquid Chromatography; Tandem Mass Spectrometry
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