Mathematical modelling was combined with experimental Cu isotope measurements to demonstrate the effect of the sample matrix in changing the absolute and relative abundances of spectral interferences from Ti and Cr species. This unforeseen non-spectral effect, evidenced by variable inaccuracies of the different Zn-normalised Cu isotope ratios, was investigated by comparing real sedimentary samples and artificial solutions intended to match the Cu:Ti:Cr ratios of the real samples after (one-or two-step) chromatographic processing. Artificial solutions showed positive bias in δ 65 Cu X/Y with the magnitude depending on (1) the 6X Zn/
6YZn ratio used for normalisation, (2) the Ti/Cu ratio and (3) the transmission Accepted Article