High-Precision Automated Workflow for Urinary Untargeted Metabolomic Epidemiology was written by Meister, Isabel;Zhang, Pei;Sinha, Anirban;Skold, C. Magnus;Wheelock, Asa M.;Izumi, Takashi;Chaleckis, Romanas;Wheelock, Craig E.. And the article was included in Analytical Chemistry (Washington, DC, United States) in 2021.Electric Literature of C5H5NO This article mentions the following:
Urine is a noninvasive biofluid that is rich in polar metabolites and well suited for metabolomic epidemiol. However, because of individual variability in health and hydration status, the physiol. concentration of urine can differ >15-fold, which can pose major challenges in untargeted liquid chromatog.-mass spectrometry (LC-MS) metabolomics. Although numerous urine normalization methods have been implemented (e.g., creatinine, sp. gr.-SG), most are manual and, therefore, not practical for population-based studies. To address this issue, we developed a method to measure SG in 96-well-plates using a refractive index detector (RID), which exhibited accuracy within 85-115% and <3.4% precision. Bland-Altman statistics showed a mean deviation of -0.0001 SG units (limits of agreement: -0.0014 to 0.0011) relative to a hand-held refractometer. Using this RID-based SG normalization, we developed an automated LC-MS workflow for untargeted urinary metabolomics in a 96-well-plate format. The workflow uses pos. and neg. ionization HILIC chromatog. and acquires mass spectra in data-independent acquisition (DIA) mode at three collision energies. Five tech. internal standards (tISs) were used to monitor data quality in each method, all of which demonstrated raw coefficients of variation (CVs) < 10% in the quality controls (QCs) and < 20% in the samples for a small cohort (n = 87 urine samples, n = 22 QCs). Application in a large cohort (n = 842 urine samples, n = 248 QCs) demonstrated CVQC < 5% and CVsamples < 16% for 4/5 tISs after signal drift correction by cubic spline regression. The workflow identified >540 urinary metabolites including endogenous and exogenous compounds This platform is suitable for performing urinary untargeted metabolomic epidemiol. and will be useful for applications in population-based mol. phenotyping. In the experiment, the researchers used many compounds, for example, Pyridin-4-ol (cas: 626-64-2Electric Literature of C5H5NO).
Pyridin-4-ol (cas: 626-64-2) belongs to pyridine derivatives. Pyridine has a dipole moment and a weaker resonant stabilization than benzene (resonance energy 117 kJ·mol−1 in pyridine vs. 150 kJ·mol−1 in benzene). Many analogues of pyridine are known where N is replaced by other heteroatoms . Substitution of one C–H in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.Electric Literature of C5H5NO