Isotope dilution is a well-known primary ratio method of quantitative analysis that yields good-quality metrological results. Many equations have been proposed to calculate the amount of substance from the isotope ratio measurements, and these have been used successfully for more than a half-century. Decades ago, isotope dilution equations were extended to correct for analyte formation during analysis, which is especially apparent in the analysis of methylmercury or chromium(VI). Considering only methods for the determination of these two analytes, many variables that are involved must be considered (for example, the extent of analyte formation, the number of isotopes monitored for each analyte, the number of substances, or the nature of mass spectra (elemental versus molecular)). To date, no master equation that can adequately address all of these aspects of the problem has been proposed. In this manuscript, we propose a general equation for isotope dilution.