A method of isotope ratio mass spectrometry comprising: flowing a liquid mobile phase through a separation device; reducing the flow rate of the mobile phase through the separation device for at least a portion of time that at least one molecular species is emerging from the separation device to achieve a desired isotope ratio precision, wherein the flow rate is reduced from a first rate to a second rate corresponding to a higher theoretical plate height of the separation device; and mass analyzing the molecular species that has emerged from the separation device at least while the flow rate is reduced; and determining at least one isotope ratio from the intensities of mass peaks of at least two isotopologues, wherein the mass analysis is performed with mass resolving power high enough to resolve the two most abundant mass peaks at the nominal mass of at least one of the isotopologues.