Kinetics of intestinal calcium absorption in humans measured using stable isotopes and high-precision thermal ionization mass spectrometry

Abstract

Oral (44Ca: 0.13-0.20 mmol) and intravenous (42Ca: 0.02-0.037 mmol) isotopically enriched stable calcium (Ca) tracers were given together with an oral dose of 2.5 mmol of natural Ca to normal subjects. Blood and urine samples were collected up to 24 h after the tracer doses and atom fractions (AFs) of these tracers (relative to natural Ca) were measured by high-precision thermal ionization mass spectrometry (TIMS). The time-dependent fractional rate of oral dose absorbed and true fractional intestinal Ca absorption (alpha) were derived from the Afs by mathematical deconvolution. After 6 h, the ratio AF oral tracer/AF intravenous tracer in blood equalled that in urine and did not change thereafter. Reproducibility of the combination of chemical precipitation of Ca (from a urine standard) and subsequent TIMS measurements, in nine runs over 13 months, was 1.2% (coefficient of variation). This was in accord with the within-run reproducibility. An estimate of alpha derived from a single blood or urine measurement was 6-10% higher than the reference value obtained by deconvolution. This discrepancy could be explained by a correction factor depending, in part, on the elapsed time for peak Ca intestinal absorption rate. Instrumentally induced mass fractionation, as well as contributions from radiogenic Ca, had a significant effect on the accuracy and reproducibility of the ratio of AFs of tracers in blood and urine.