Carbon Isotopes Profiles of Human Whole Blood, Plasma, Red Blood Cells, Urine and Feces for Biological/Biomedical 14C-Accelerator Mass Spectrometry Applications

Radiocarbon (14C) is an ideal tracer for in vivo human ADME (absorption, distribution, metabolism, elimination) and PBPK (physiological-based pharmacokinetic) studies. Living plants peferentially incorporate atmospheric 14CO2 versus 13CO2 versus 12CO2, which result in unique signature. Furthermore, plants and the food chains they support also have unique carbon isotope signatures. Humans, at the top of the food chain, consequently acquire isotopic concentrations in the tissues and body fluids depending on their dietary habits. In preparation of ADME and PBPK studies, 12 healthy subjects were recruited. The human baseline (specific to each individual and their diet) total carbon (TC) and carbon isotope 13C (δ13C) and 14C (F m) were quantified in whole blood (WB), plasma, washed red blood cell (RBC), urine, and feces. TC (mg of C/100 μL) in WB, plasma, RBC, urine, and feces were 11.0, 4.37, 7.57, 0.53, and 1.90, respectively. TC in WB, RBC, and feces was higher in men over women, P < 0.05. Mean δ13C were ranked low to high as follows: feces < WB = plasma = RBC = urine, P < 0.0001. δ13C was not affected by gender. Our analytic method shifted δ13C by only ±1.0 ‰ ensuring our F m measurements were accurate and precise. Mean F m were ranked low to high as follows: plasma = urine < WB = RBC = feces, P < 0.05. F m in feces was higher for men over women, P < 0.05. Only in WB, 14C levels (F m) and TC were correlated with one another (r = 0.746, P < 0.01). Considering the lag time to incorporate atmospheric 14C into plant foods (vegetarian) and or then into animal foods (nonvegetarian), the measured F m of WB in our population (recruited April 2009) was 1.0468 ± 0.0022 (mean ± SD), and the F m of WB matched the (extrapolated) atmospheric F m of 1.0477 in 2008. This study is important in presenting a procedure to determine a baseline for a study group for human ADME and PBPK studies using 14C as a tracer.