title: Statistical procedures for the determination of linearity, detection limits and measurement uncertainty: A deeper look into SPE-LC-Orbitrap mass spectrometry of pharmaceuticals in wastewater.
abstract: This research addresses some critical challenges regarding the validation of a quantitative multi-residue method for pharmaceuticals in wastewater making use of modern SPE-LC-Orbitrap high-resolution mass spectrometry. Particular attention is given to study in detail response linearity, to realistically estimate detection limits, and to express the measurement precision of the analyte concentration, obtained by external calibration. First, linearity of the Orbitrap response showed to be matrix dependent in a counter intuitive way: stronger deviations from linearity were observed for pure solvent standards than for complex matrices like wastewater. Second, detection limits risk to be overestimated for ubiquitously present compounds for which true blank matrix samples are hard to find, leading to false negative findings. A novel and easy applicable methodology is presented to allow a better estimation of detection limits using the response of the natural isotopes. Third, a statistical methodology to estimate the measurement precision of the analyte concentration using basic validation parameters is developed specifically for the context of multi-residue quantification.
authors.affiliation: Research Group Environmental Organic Chemistry and Technology (EnVOC), Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
authors.forename: Leendert
authors.initials: L
authors.lastname: Vergeynst
authors.affiliation: Research Group Environmental Organic Chemistry and Technology (EnVOC), Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
authors.forename: Kenneth
authors.initials: K
authors.lastname: K'oreje
authors.affiliation: Research Group Environmental Organic Chemistry and Technology (EnVOC), Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: De Wispelaere
authors.affiliation: Research Group Environmental Organic Chemistry and Technology (EnVOC), Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
authors.forename: Lies
authors.initials: L
authors.lastname: Harinck
authors.affiliation: Research Group Environmental Organic Chemistry and Technology (EnVOC), Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Van Langenhove
authors.affiliation: Research Group Environmental Organic Chemistry and Technology (EnVOC), Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium. Electronic address: Kristof.Demeestere@UGent.be.
authors.forename: Kristof
authors.initials: K
authors.lastname: Demeestere
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000706:statistics & numerical data*; D057230:Limit of Detection; D016014:Linear Models; D013058:Mass Spectrometry / Q000706:statistics & numerical data*; D004364:Pharmaceutical Preparations / Q000032:analysis*; D015203:Reproducibility of Results; D052616:Solid Phase Extraction / Q000706:statistics & numerical data*; D035501:Uncertainty; D062065:Wastewater / Q000032:analysis*; D014874:Water Pollutants, Chemical / Q000032:analysis*
chemical_list: D004364:Pharmaceutical Preparations; D062065:Wastewater; D014874:Water Pollutants, Chemical
keywords: Detection limit; High-resolution mass spectrometry; Linearity; Measurement uncertainty; Validation