Measurement of trimethylamine-N-oxide by stable isotope dilution liquid chromatography tandem mass spectrometry |
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Authors: | Zeneng Wang Bruce S Levison Jennie E Hazen Lillian Donahue Xin-Min Li Stanley L Hazen |
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Affiliation: | 1. Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA;2. Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH 44195, USA |
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Abstract: | Trimethylamine-N-oxide (TMAO) levels in blood predict future risk for major adverse cardiac events including myocardial infarction, stroke, and death. Thus, the rapid determination of circulating TMAO concentration is of clinical interest. Here we report a method to measure TMAO in biological matrices by stable isotope dilution liquid chromatography tandem mass spectrometry (LC/MS/MS) with lower and upper limits of quantification of 0.05 and >200 μM, respectively. Spike and recovery studies demonstrate an accuracy at low (0.5 μM), mid (5 μM), and high (100 μM) levels of 98.2, 97.3, and 101.6%, respectively. Additional assay performance metrics include intraday and interday coefficients of variance of <6.4 and <9.9%, respectively, across the range of TMAO levels. Stability studies reveal that TMAO in plasma is stable both during storage at −80 °C for 5 years and to multiple freeze thaw cycles. Fasting plasma normal range studies among apparently healthy subjects (n = 349) show a range of 0.73–126 μM, median (interquartile range) levels of 3.45 (2.25–5.79) μM, and increasing values with age. The LC/MS/MS-based assay reported should be of value for further studies evaluating TMAO as a risk marker and for examining the effect of dietary, pharmacologic, and environmental factors on TMAO levels. |
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Keywords: | Trimethylamine-N-oxide Cardiovascular disease Mass spectrometry |
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