Different calibration approaches including external calibration, standard addition and internal standard are evaluated for quantification of coeluted compounds in liquid chromatography with MS spectrometry detection in scan mode and using multivariate curve resolution. These different calibration approaches are proposed to cope with sensitivity changes and matrix effects encountered in the analysis of complex natural environmental samples. By using them, multivariate curve resolution analysis of MS data in scan mode gave similar quantitative results to those obtained by LC-MS in selected ion monitoring (SIM) mode (in both cases errors were below 16% for internal standard combined with standard addition strategy), and it provided at the same time a means of analyte confirmation via their resolved pure MS spectra, and a means to gather a larger amount of information about the whole chromatographic process and to facilitate the simultaneous determination of multiple analytes in the same chromatographic run using the same experimental and instrumental conditions.