Comparative measurements of total body water in healthy volunteers by online breath deuterium measurement and other near-subject methods

Abstract

FA-MS is a simple and effective new approach to TBW measurement in healthy subjects. The difficulty of using population-derived equations to estimate TBW in individual subjects is emphasized.

Breath biomarkers in toxicology

“…Most of the novel tests employ organic compounds with isotopically labeled carbon-13 ( 13 C), oxygen-18 ( 18 O), or deuterium ( 2 H), wherein a more complex organic probe molecule with these substitutions is injected into or ingested by the patient (Schellekens et al 2011). Exhaled breath is then monitored using mass spectrometry or optical instrumentation for perturbations in the normal isotopic abundances of water or CO 2 that would indicate metabolism of the probe (Smith et al 2002;Crosson et al 2002;Logan et al 1991). Of particular note in this category is the helicobacter pylori CO 2 breath test based on ingestion of 13 C-labeled urea, which has become a standard noninvasive alternative method for identifying an underlying cause of gastric and duodenal ulcers (Cutler et al 1995).…”

Determination of the Deuterium Abundances in Water from 156 to 10,000 ppm by SIFT-MS

“…they contain just one 18 O atom and an insignificant fraction of D atoms). We have shown that these requirements are met when the deuterium abundance in the water vapour to be analysed is less than 1000 ppm and using FA-MS in this regime we have made many measurements on TBW in healthy controls and dialysis patients that demonstrate its validity [5][6][7]. But above about 1000 ppm an increasing fraction of the m/z 75 ions become populated with a single D atom in combination with a single 17 O atom and/or two D atoms (see Figure 1 later), and this added complication must then be taken into account in order to obtain accurate deuterium abundances.…”

“…This allowed the TBW in human subjects to be determined to a comparable precision and accuracy (but see the important proviso and development described in the next paragraph). Much work in the measurement of TBW has been accomplished in collaboration with our clinical colleagues using FA-MS [5][6][7][15][16][17]. However, this method does have a weakness in that by avoiding the upstream mass filter and directly discharging the helium carrier gas/water vapour mixture (which inevitably contains traces of air), ions like NO + and O 2 + are formed in addition to H 3 O + and its hydrates.…”

“…the ratio of the number of D atoms to the total number of atoms of all hydrogen isotopes), from which the D abundance in the associated liquid water phase can be derived [2][3][4]. Research has focused on the measurement of total body water (TBW) by analysing exhaled breath for HDO following the ingestion of an accurate amount of pure D 2 O, exploiting the principle of isotope dilution [4,5]. Thus, the ingested D 2 O rapidly becomes HDO via fast isotopic exchange with the abundant body water molecules and after some time, typically 100 min, the HDO is equilibrated throughout the body water, which is reflected in its level in the exhaled water vapour.…”

Implications of the variability in time to isotopic equilibrium in the deuterium dilution technique

“…Although multiple post-dose samples can be collected, more commonly a single post-dose sample is provided at a time when isotopic enrichment has been reached within the body fluid. Sampling mediums include blood, saliva, urine and, more recently, measures of expired air (Smith et al, 2002). The timing of the post-dose sample collection is not the same for each sampling medium as the time to reach isotopic equilibrium is longer when urine is the sampling medium.…”