Quantitative Mass Spectrometry Independence from Matrix Effects and Detector Saturation Achieved by Flow Injection Analysis with Real-Time Infinite Dilution NanitaSergio C. 2013 A high-throughput quantitative analysis method is presented to determine analyte concentrations at the infinite dilution limit, where the presence and effects of matrix become null, achieving mathematical independence from the detrimental phenomenon of matrix effects. Dilution is achieved online, reproducibly and in seconds by diffusion/mixing that occurs in flow injection analysis, while analyte concentration measurements are made by electrospray ionization tandem mass spectrometry. Because of matrix effects, the measured analyte concentration (<i>A</i><sub>m</sub>) was inaccurate at high matrix concentrations, but accuracy consistently improved as matrix concentration was reduced by dilution. The method provides a practical solution around the decades-long matrix effects problem in quantitative analytical chemistry without separation of analytes from the matrix (e.g., chromatography) or use of corrective procedures, such as matrix-matched standards or isotopically labeled internal standards. Broad applications were demonstrated for part-per-billion quantitation of bioactive molecules (pesticides) in extracts of food, plant tissues, and body fluids by coupling the method to a high-throughput sample extraction/cleanup based on salting out with ammonium formate. The technique provides an assessment of matrix effects with remarkable comprehensiveness, simplicity, and speed. A limit of quantitation of 10 ng/g, a level appropriate for pesticide residue analysis and bioanalytical applications, was demonstrated. The method is also independent of detector saturation; this feature increased the applicable concentration range 20–100-fold above that of conventional techniques. In the abstract graphic, the measured analyte concentration (<i>A</i><sub>m</sub>) approaches the accurate value (<i>A</i><sub>0</sub>) when matrix effects disappear as measurements are conducted while lowering the normalized sample concentration (<i>S</i><sub>norm</sub>) by real-time dilution.