A method of operating an isotope ratio spectrometer for measurement of a sample, comprising: measuring first isotope ratios and first signal intensities for a first reference in the spectrometer, over a first measurement time period, a first relationship comprising a relationship between the first isotope ratios and the first signal intensities being determined; measuring sample isotope ratios and sample signal intensities in the spectrometer, over a second measurement time period subsequent to the first measurement time period; measuring second isotope ratios and second signal intensities for a second reference in the spectrometer, over a third measurement time period subsequent to the second measurement time period, a second relationship comprising a relationship between the second isotope ratios and the second signal intensities being determined; establishing a time A within the first time period, at which a signal intensity for the first reference matches a signal intensity for the sample at time X and thereby identify a first reference isotope ratio for the time A, using the first relationship; establishing a time B within the third time period, at which a signal intensity for the second reference matches a signal intensity for the sample at time X and thereby identify a second reference isotope ratio for the time B, using the second relationship; estimating a reference isotope ratio for a time X within the second measurement time period based on the time X, the first reference isotope ratio for the time A, the time A, the second reference isotope ratio for the time B and the time B; and wherein the first and second references have the same chemical composition as the sample. measuring first isotope ratios and first signal intensities for a first reference in the spectrometer, over a first measurement time period, a first relationship comprising a relationship between the first isotope ratios and the first signal intensities being determined; measuring sample isotope ratios and sample signal intensities in the spectrometer, over a second measurement time period subsequent to the first measurement time period; measuring second isotope ratios and second signal intensities for a second reference in the spectrometer, over a third measurement time period subsequent to the second measurement time period, a second relationship comprising a relationship between the second isotope ratios and the second signal intensities being determined; establishing a time A within the first time period, at which a signal intensity for the first reference matches a signal intensity for the sample at time X and thereby identify a first reference isotope ratio for the time A, using the first relationship; establishing a time B within the third time period, at which a signal intensity for the second reference matches a signal intensity for the sample at time X and thereby identify a second reference isotope ratio for the time B, using the second relationship; estimating a reference isotope ratio for a time X within the second measurement time period based on the time X, the first reference isotope ratio for the time A, the time A, the second reference isotope ratio for the time B and the time B; and wherein the first and second references have the same chemical composition as the sample.