High mass accuracy assay for trimethylamine N-oxide using stable-isotope dilution with liquid chromatography coupled to orthogonal acceleration time of flight mass spectrometry with multiple reaction monitoring

Heaney, Liam M.; Jones, Donald J. L.; Mbasu, Richard J.; Ng, Leong L.; Suzuki, Toru

doi:10.1007/s00216-015-9164-6

Cited by 37 publications

(25 citation statements)

References 31 publications

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“…[12,13,17,20,24] Comparison of predictive ability against other biomarkers that had been previously assessed in this cohort (NT-proBNP, copeptin, PENK, MR-proADM, pro-SP), [4][5][6][7] showed that TMAO retained independent predictive ability after adjustment for them. Interestingly, NTproBNP, as a golden standard benchmark biomarker for prediction of adverse outcomes following acute MI, [25] was not able to retain independent prediction for adverse outcome in this cohort at 2 years.…”

Section: Discussionmentioning

confidence: 85%

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Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction

et al. 2017

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Section: Discussionmentioning

confidence: 85%

“…[24] Briefly, protein precipitation was performed by adding 80 µL deuterated TMAO (D9-, 10 µmol/L) to 20 µL of plasma. Extracted samples were analyzed using hydrophilic interaction liquid chromatography-time of flight mass spectrometry with multiple reaction monitoring.…”

Section: Biomarker Measurementsmentioning

confidence: 99%

Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction

et al. 2017

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“…Plasma TMAO was extracted using stable-isotope dilution and analysed by ultraperformance liquid chromatography-mass spectrometry, with previously reported techniques 16. A brief explanation of these methods is described in the online supplementary material.…”

Section: Methodsmentioning

confidence: 99%

TrimethylamineN-oxide and prognosis in acute heart failure

Suzuki

Heaney

Bhandari

et al. 2016

Heart

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Objective Acute heart failure (AHF) is associated with high mortality and morbidity. Trimethylamine N-oxide (TMAO), a gut-derived metabolite, has reported association with mortality risk in chronic HF but this association in AHF is still unknown. The present study investigated TMAO in patients admitted to hospital with AHF, and association of circulating levels with prognosis. Methods In total, 972 plasma samples were analysed for TMAO concentration by liquid chromatography-mass spectrometry. Associations with in-hospital mortality (72 events), all-cause mortality (death, 268 events) and a composite of death or rehospitalisation due to HF (death/HF, 384 events) at 1 year were examined. Results TMAO improved risk stratification for inhospital mortality in combination with current clinical scorings (OR≥1.13, p≤0.014). TMAO tertile analyses reported a graded risk in adverse outcome within 1 year (OR≥1.61, p≤0.004) and improved outcome prediction when stratified as none, one or both biomarker(s) elevated in combination with N-terminal pro B-type natriuretic peptide (NT-proBNP) (OR≥2.15, p≤0.007). TMAO was independently predictive for death and death/ HF when corrected for cardiac risk factors (HR≥1.16, p≤0.037); however, this ability was weakened when indices of renal function were included, possibly due to multicollinearity. Conclusions TMAO contributed additional information on patient stratification for in-hospital mortality of AHF admissions using available clinical scores that include renal indices. Furthermore, elevated levels were associated with poor prognosis at 1 year and combination of TMAO and NT-proBNP provided additional prognostic information. TMAO was a univariate predictor of death and death/HF, and remained an independent predictor until adjusted for renal confounders.

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“…Several mass spectrometry (MS) based methodologies that quantify TMAO have been reported [21–24]. While sensitive and rapid, they require use of a synthetic stable isotope labeled internal standard, uniquely trained personnel, and specialized and expensive equipment not always available in the clinical diagnostic laboratory.…”

Section: Introductionmentioning

confidence: 99%

NMR quantification of trimethylamine- N -oxide in human serum and plasma in the clinical laboratory setting

Garcia¹,

Wolak-Dinsmore²,

Wang

et al. 2017

Clinical Biochemistry

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Background and objectives Trimethylamine-N-oxide (TMAO) produced by gut microbiota metabolism of dietary choline and carnitine has been shown to be associated with increased risk of cardiovascular disease (CVD) and to provide incremental clinical prognostic utility beyond traditional risk factors for assessing a patient’s CVD risk. The aim of this study was to develop an automated nuclear magnetic resonance (NMR) spectroscopy assay for quantification of TMAO concentration in serum and plasma using a high-throughput NMR clinical analyzer. Methods Key steps in assay development included: (i) shifting the TMAO analyte peak to a less crowded region of the spectrum with a pH buffer/reagent, (ii) attenuating the broad protein background signal in the spectrum and (iii) using a non-negative least squares algorithm for peak deconvolution. Assay performance was evaluated according to Clinical and Laboratory Standards Institute guidelines. A method comparison study was performed to compare TMAO concentrations quantified by NMR and mass spectrometry (MS). Results The within-run and within-lab imprecision ranged from 4.3 to 14.5%. Under the acquisition method employed, the NMR assay had a limit of blank, detection and quantitation of 1.6, 3.0 and 3.3 μM, respectively. Linearity was demonstrated within the reportable range of 3.3 to 3,000 μM. TMAO measurements using the NMR assay, which involves minimal sample preparation, compared well with values obtained with the MS-based assay (R2 = 0.98). Conclusions The NMR based assay provides a simple and accurate measurement of circulating TMAO levels amenable to the high-throughput demands of the clinical chemistry laboratory. Moreover, assay performance enables the levels of TMAO to be quantified in serum or plasma at clinically actionable concentrations for the assessment of cardiovascular disease risks and individualized dietary monitoring.

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High mass accuracy assay for trimethylamine N-oxide using stable-isotope dilution with liquid chromatography coupled to orthogonal acceleration time of flight mass spectrometry with multiple reaction monitoring

Abstract: Abstract.Background: Trimethylamine N-oxide (TMAO) has attracted interest as circulating levels have

Cited by 37 publications

References 31 publications

Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction

Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction

TrimethylamineN-oxide and prognosis in acute heart failure

NMR quantification of trimethylamine- N -oxide in human serum and plasma in the clinical laboratory setting

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