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

摘要

Radiocarbon (¹⁴C) is an ideal tracer for in vivo human ADME (absorption, distribution, metabolism, elimination) and PBPK (physiological-based pharmacokinetic) studies. Living plants preferentially incorporate atmospheric ¹⁴CO2, vs ¹³CO2, vs 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 (Fm) were quantified in whole blood (WB), plasma, washed red blood cell (RBC), urine, and feces. TC (mg of C/100μL) 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 Fm measurements were accurate and precise. Mean Fm were ranked low to high as follows, plasma = urine < WB = RBC = feces, P < 0.05. Fm in feces was higher for men over women, P < 0.05. Only in WB, ¹⁴C levels (Fm) 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 (non-vegetarian), the measured Fm of WB in our population (recruited April 2009) was 1.0468 ± 0.0022 (mean±SD), the Fm of WB matched the (extrapolated) atmospheric Fm 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.