title: Simultaneous determination of trimethylamine and trimethylamine N-oxide in mouse plasma samples by hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry.
abstract: A method was developed that applies hydrophilic interaction liquid chromatography with tandem mass spectrometry in the multiple reaction monitoring mode to separate and accurately quantify trimethylamine and trimethylamine N-oxide in a single chromatographic run. This was achieved by converting trimethylamine to ethyl betaine, which is less volatile and hence results in greatly improved quantitation. Ethyl betaine also gives a similar response to trimethylamine N-oxide using positive-ion electrospray ionization mass spectrometry. It is readily separated from trimethylamine N-oxide by hydrophilic liquid chromatography in a 5 min run and with improved peak shape compared to underivatized trimethylamine. Validation of the method yielded a limit of detection (S/N ≥ 3) of 0.5 ng/mL for trimethylamine and 0.25 ng/mL for trimethylamine N-oxide. Method accuracies of 91.4-105.3% with precisions of 0.4-5.5% were obtained for standard mixtures over the range of 2.5-500 ng/mL. Recoveries measured for the extraction of trimethylamine and trimethylamine N-oxide spikes into mouse plasma were both >90%. The method, which simultaneously measures trimethylamine and trimethylamine N-oxide, was successfully applied to mouse plasma samples and could be adapted for use with other biological fluids.
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
authors.forename: Si
authors.initials: S
authors.lastname: Mi
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhao
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
authors.forename: René L
authors.initials: RL
authors.lastname: Jacobs
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Curtis
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods*; D002853:Chromatography, Liquid; D057927:Hydrophobic and Hydrophilic Interactions; D057230:Limit of Detection; D008744:Methylamines / Q000097:blood*; D051379:Mice; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: D008744:Methylamines; C005855:trimethyloxamine; C023336:trimethylamine
keywords: derivatization; hydrophilic interaction chromatography; tandem mass spectrometry; trimethylamine; trimethylamine N-oxide