A QTrap 6500+ mass spectrometer equipped with an electrospray ionization (ESI) source (Sciex) was operated using one of our previously published multiple reaction monitoring (MRM) methods with fast polarity switching . Full method parameters including MRM transitions and ESI parameters are detailed in the SI. Non-targeted HRMS(/MS). An Orbitrap Exploris 480 mass spectrometer (Thermo) was used for the high-resolution measurements. Samples were analyzed using full scan mode and AcquireX was used to generate fragment spectra using a mass resolution of 120,000 at m/z 200, with full method parameters reported in the SI. Data Analysis Quality Control. Several types of QC samples were used to ensure reliable results. A systems suitability test sample (SST) was measured before and after each analytical sequence to ensure favorable instrument performance (see SI and Table ). In addition, a multi-analyte reference standard mixture consisting of 94 highly diverse chemicals in pure solvent was injected. Solvent blanks were used to monitor instrumental background and carry-over and process blanks were used to monitor background concentrations/contaminations. Targeted Data Analysis. RE and SSE values were evaluated for the set of 94 analytes 6 using standards in neat solvent, pooled urine, and pooled plasma. Peak integration was carried out using Multiquant (v3.0.2, Sciex) and Skyline (v21.2.2.536, McCoss Lab) . Calculation of RE and SSE was performed using Microsoft Office 365. Graphics were created by Origin 2021b (v9.8; OriginLab Corporation). Non-targeted Data Analysis. Raw data files acquired in polarity switching mode were separated based on the polarity using Freestyle (Thermo). Then, the data files including MS1 and MS2 spectra, were analyzed using MSDIAL (v5.2) . Full data processing settings including data extraction, peak picking, compound identification, and alignment are reported in the SI. To evaluate the qualitative analyte coverage for NTA and suspect screening, MassBank of North America (MoNA, ) was used as a spectral library. Annotations were then classified based on the level of confidence according to Schymanski et al. using confidence levels 1 (confirmed by authentic standards), level 2 (confirmed by spectral library match), and level 3 (confirmed by spectral library match, but with isomeric structures). Additional data analysis and data visualization were performed using Microsoft Office 365, Origin 2021b, MetaboAnalyst (v6.0), and Inkscape (version 1.2.2; Inkscape).