title: Accurate mass determination, quantification and determination of detection limits in liquid chromatography-high-resolution time-of-flight mass spectrometry: challenges and practical solutions.
abstract: Uniform guidelines for the data processing and validation of qualitative and quantitative multi-residue analysis using full-spectrum high-resolution mass spectrometry are scarce. Through systematic research, optimal mass accuracy and sensitivity are obtained after refining the post-processing of the HRMS data. For qualitative analysis, transforming the raw profile spectra to centroid spectra is recommended resulting in a 2.3 fold improved precision on the accurate mass determination of spectrum peaks. However, processing centroid data for quantitative purposes could lead to signal interruption when too narrow mass windows are applied for the construction of extracted ion chromatograms. Therefore, peak integration on the raw profile data is recommended. An optimal width of the mass window of 50 ppm, which is a trade-off between sensitivity and selectivity, was obtained for a TOF instrument providing a resolving power of 20,000 at full width at half maximum (FWHM). For the validation of HRMS analytical methods, widespread concepts such as the signal-to-noise ratios for the determination of decision limits and detection capabilities have shown to be not always applicable because in some cases almost no noise can be detected anymore. A statistical methodology providing a reliable alternative is extended and applied.
authors.affiliation: Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.
authors.forename: Leendert
authors.initials: L
authors.lastname: Vergeynst
authors.forename: Herman
authors.initials: H
authors.lastname: Van Langenhove
authors.forename: Pieter
authors.initials: P
authors.lastname: Joos
authors.forename: Kristof
authors.initials: K
authors.lastname: Demeestere
mesh_terms: D000465:Algorithms; D002853:Chromatography, Liquid / Q000379:methods*; D057230:Limit of Detection; D013058:Mass Spectrometry / Q000379:methods*; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000032:analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D059629:Signal-To-Noise Ratio; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D014874:Water Pollutants, Chemical / Q000032:analysis
chemical_list: D004364:Pharmaceutical Preparations; D014874:Water Pollutants, Chemical
keywords: Accurate mass; High-resolution mass spectrometry; Mass window width; Micropollutants; Pharmaceuticals; Validation