Nontarget analysis (NTA) by liquid chromatography coupled to high-resolution mass spectrometry improves the capacity to comprehend the molecular composition of complex mixtures compared to targeted analysis techniques. However, the detection of unknown compounds means that quantification in NTA is challenging. This study proposes a new semi-quantitative methodology for use in the NTA of organic aerosol. Quantification of unknowns is achieved using the average ionization efficiency of multiple quantification standards which elute within the same retention time window as the unknown analytes. In total, 110 authentic standards constructed 25 retention time windows for the quantification of oxygenated (CHO) and organonitrogen (CHON) species. The method was validated on extracts of biomass burning organic aerosol (BBOA) and compared to quantification with authentic standards and had an average prediction error of 1.52 times. Furthermore, 70% of concentrations were estimated within a factor of 2 (prediction errors between 0.5 and 2 times) from the authentic standard quantification. The semi-quantification method also showed good agreement for the quantification of CHO compounds compared to predictive ionization efficiency-based methods, whereas for CHON species, the prediction error of the semi-quantification method (1.63) was significantly lower than the predictive ionization efficiency approach (14.94). Application to BBOA for the derivation of relative abundances of CHO and CHON species showed that using peak area underestimated the relative abundance of CHO by 19% and overestimated that of CHON by 11% compared to the semi-quantification method. These differences could lead to significant misinterpretations of source apportionment in complex samples, highlighting the need to account for ionization differences in NTA approaches.