A method for determining a quantity of an analyte in a liquid sample, comprising: adding a known quantity of an internal standard comprising an isotopically labeled version of the analyte to the sample; providing a continuous stream of the sample having the internal standard to an inlet of a Liquid Chromatography Mass Spectrometry (LCMS) system comprising a chromatograph fluidically coupled to a mass spectrometer, whereby the chromatograph separates the stream into chemical separates that are received by and ionized by the mass spectrometer, the ionization generating a plurality of precursor ion species; and repeatedly performing the steps of: performing (106, 113) a data-independent analysis of the precursor ion species using a mass analyzer, whereby mass spectra of a plurality of product-ion species generated by fragmentation of the precursor ion species are acquired; calculating, from the results of one or more of the data-independent analyses, one or more degree-of-matching scores that relate to either a number of ions of the internal standard that are detected or to overlap between results of the data-independent analysis and tabulated mass spectral data of the internal standard; and if each of the degree-of-matching scores meets a respective degree-of-matching condition, performing a targeted quantitative tandem mass spectrometric analysis of the internal standard and a quantitative tandem mass spectrometric analysis of the analyte using a mass spectrometer of the LCMS system; and calculating the quantity of the analyte in the sample by comparison between intensities of one or more mass spectral signals generated by the quantitative tandem mass spectrometric analyses of the analyte to intensities of one or more mass spectral signals generated by the targeted quantitative tandem mass spectrometric analyses of the internal standard. adding a known quantity of an internal standard comprising an isotopically labeled version of the analyte to the sample; providing a continuous stream of the sample having the internal standard to an inlet of a Liquid Chromatography Mass Spectrometry (LCMS) system comprising a chromatograph fluidically coupled to a mass spectrometer, whereby the chromatograph separates the stream into chemical separates that are received by and ionized by the mass spectrometer, the ionization generating a plurality of precursor ion species; and repeatedly performing the steps of: performing (106, 113) a data-independent analysis of the precursor ion species using a mass analyzer, whereby mass spectra of a plurality of product-ion species generated by fragmentation of the precursor ion species are acquired; calculating, from the results of one or more of the data-independent analyses, one or more degree-of-matching scores that relate to either a number of ions of the internal standard that are detected or to overlap between results of the data-independent analysis and tabulated mass spectral data of the internal standard; and if each of the degree-of-matching scores meets a respective degree-of-matching condition, performing a targeted quantitative tandem mass spectrometric analysis of the internal standard and a quantitative tandem mass spectrometric analysis of the analyte using a mass spectrometer of the LCMS system; and performing (106, 113) a data-independent analysis of the precursor ion species using a mass analyzer, whereby mass spectra of a plurality of product-ion species generated by fragmentation of the precursor ion species are acquired; calculating, from the results of one or more of the data-independent analyses, one or more degree-of-matching scores that relate to either a number of ions of the internal standard that are detected or to overlap between results of the data-independent analysis and tabulated mass spectral data of the internal standard; and if each of the degree-of-matching scores meets a respective degree-of-matching condition, performing a targeted quantitative tandem mass spectrometric analysis of the internal standard and a quantitative tandem mass spectrometric analysis of the analyte using a mass spectrometer of the LCMS system; and calculating the quantity of the analyte in the sample by comparison between intensities of one or more mass spectral signals generated by the quantitative tandem mass spectrometric analyses of the analyte to intensities of one or more mass spectral signals generated by the targeted quantitative tandem mass spectrometric analyses of the internal standard.