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

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• 作者：Seung-Hyun Kim ; Jennifer C. Chuang ; Peter B. Kelly ; Andrew J. Clifford
• 刊名：Analytical Chemistry
• 出版年：2011
• 出版时间：May 1, 2011
• 年：2011
• 卷：83
• 期：9
• 页码：3312-3318
• 全文大小：775K
• 年卷期：v.83,no.9(May 1, 2011)
• ISSN：1520-6882

文摘

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 (未¹³C) and ¹⁴C (F_m) were quantified in whole blood (WB), plasma, washed red blood cell (RBC), urine, and feces. TC (mg of C/100 渭L) 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 未¹³C were ranked low to high as follows: feces < WB = plasma = RBC = urine, P < 0.0001. 未¹³C was not affected by gender. Our analytic method shifted 未¹³C by only 卤1.0 鈥?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 卤 0.0022 (mean 卤 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.