Precise and accurate determination of calcium isotope ratios in urine is imperative in limiting the expense of enriched isotopes used in human metabolic tracer studies. The calcium isotope spectrum obtained from an ICP-MS (using conventional spray chamber), operated in low resolution mode (LR = 300), is subject to numerous polyatomic, isobaric and doubly charged interferences. The most severe polyatomic interfences can be resolved at resolutions greater than 3500, whereas, isobaric and doubly charged interferences are easily corrected. Precise (<0.1% 1σ) isotope ratios, however, are not routinely obtained in medium resolution (MR = 4300). Here we use a HR-ICP-MS in MR to identify and determine methods to reduce polyatomic interferences. Using oxalate precipitation of urinary calcium and desolvation sample introduction, interferences can be reduced sufficiently to allow determination of the 42, 43, 44, 46 and 48 isotopes of calcium with the precision of LR. Isotope ratio precision and accuracy is < ±0.1%
(1σ) for analysis of three isotopes (42, 43, and 44), as required for clinical studies. Propagating this level of uncertainty indicates that >4% enrichments provide < ±10%
(2σ) uncertainty in the calculated fractional calcium absorption values. Minimizing unnecessary enrichments can increase the number of subjects in studies without increasing the substantial cost of enriched isotopes. This new analytical method is applied to our on-going clinical trials where 0.017 mg kg−1 of 42Ca (90.8%; intravenous, IV) and 0.012 mg kg−143Ca (52.1%;oral) administered to postmenopausal women show average 24 h (pooled) urinary enrichments of 5.0% and 5.1% from the intravenous and oral doses, respectively.