Abstract
Improved instrumentation and the increased availability of labeled compounds have democratized the application of isotope-dilution (tracer) methodology in nutrient metabolism. Still, the most challenging aspects of tracer experimentation reside in the steps that precede the measurement of an isotopically labeled tracer, i.e. the design of a suitably labeled tracer and its isolation and purification from complex biological matrices. Construction of useful mathematical models of nutrient dynamics require methodologies that guarantee that the integrity of the tracer is maintained across the entire sampling and analyte isolation protocol. The ability to provide accurate and reliable data highlights a need for analytical chemists to play a central role in these studies. In this regard, examples and discussion of issues relevant to stable-isotope experimentation are provided.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bier DM. The use of stable isotopes in metabolic investigation. Bailliere’s Clin Endocrinol Metab, 1987, 4:817–836.
Budzikiewicz H. Mass spectra of carotenoids — Labelling studies, in: Carotenoid Chemistry and Biochemistry. Britton G; Goodwin TW; Eds. Pergamon Press: Oxford, U.K. 1982. pp. 155–65.
Buttrill SE Jr; Shaffer B; Karnicky J; Arnold JT. Selected ion trapping to increase sensitivity for low level samples in complex matrices. Proc 40th ASMS Conf Mass Spectrom Allied Topics. Washington DC. 1992. pp. 1015-1016.
Cobelli C; Toffolo G; Bier DM; Nosadini R. Models to interpret kinetic data in stable isotope tracer studies. Am J Phys, 1987, 253:E551–564.
Dueker SR; Jones AD; Smith GM; Clifford AJ. Stable isotope methods for the study of beta-carotene-d8 metabolism in humans utilizing tandem mass spectrometry and high-performance liquid chromatography. Anal Chem, 1994, 66(23):4177–85.
Dueker SR; Jones AD; Smith GM; Clifford AJ. Preparation of [2′,3′,5′,6′-2H4]Pteroylglutamic acid. J abeled Comp Radiopharm, 1995, 36, 10:981–991.
Dueker SR; Lunetta JM; Jones AD; Clifford AJ. Solid-phase extraction protocol for isolating retinol-d4 and retinol from plasma for parallel processing for epidemiological studies. Clin Chem, 1993, 39:2318–22.
Dueker SR; Mercer, RS; Jones, AD; Clifford, AJ. An ion trap method for determination of retinol-d4 at low enrichments. Anal Chem, (in press).
Evans EA. Isotopic labeling with carbon-14 and tritium, in: Principles of Radiopharmacology. Colombetti LG; Ed. CRC Press: Boca Raton. 1979. pp. 11–25.
Geng X; Regnier FE. Stoichiometric displacement of solvent by non-polar solutes in reversed-phase liquid chromatography. J Chromatog, 1985, 332:147–168.
Green JM. A practical guide to analytical method validation. Anal Chem, 1996, 68:A305–A309.
Gregg CT; Hutson JY; Prine JR; Ott DG; Furchner JE. Substantial replacement of mammalian body carbon with carbon-13. Life Sci, 1973, 13(7):775–82.
Gregory JF 3d; Bailey LB; Toth JP; Cerda JJ. Stable-isotope methods for assessment of folate bioavailability. Am J Clin Nut, 1990, 51(2):212–5.
Guo Z K; Nielsen S; Burguera B; Jensen MD. Free fatty acid turnover measured using ultralow doses of [U-13C]palmitate. J Lipid Res, 1997, 38, 1888–1895.
Handelman GJ; Haskell MJ; Jones AD; Clifford AJ. An improved protocol for determining ratios of retinol-d4 to retinol isolated from human plasma. Anal Chem, 1993, 65(15):2024–2028.
Katz JJ; Crespi HL. Isotope effects in Biological Systems, in: Isotope Effects in Chemical Reactions. Series title: ACS monograph, 167. Collins CJ; Bowman NS; Eds. Van Nostrand Reinhold: New York. 1970. pp. 286–363.
Koletzko B; Sauerwald T; Demmelmair H. Safety of stable isotope use. Eur J Pediatr, 1997, 156:S12–7.
Korzekwa KR; Gillette JR; Trager WF. Isotope effect studies on the cytochrome P450 enzymes. Drug Metab Rev, 1995, 27(l-2):45–59.
Lowry TH; Richardson KS. Mechanism and Theory in Organic Chemistry. 3rd Ed. Harper & Row: New York. 1987.
March RE; Todd JFJ. Practical Aspects of Ion Trap Mass Spectrometry. Vol. I-III. CRC Press: New York. 1996.
Metges CC; Petzke KJ. Measurement of 15N/14N isotopic composition in individual plasma free amino acids of human adults at natural abundance by gas chromatography-combustion isotope ratio mass spectrometry. Anal Biochem, 1997, 247(1): 158–64.
Novotny JA; Dueker SR; Zech LA; Clifford AJ. Compartmental analysis of the dynamics of beta-carotene metabolism in an adult volunteer. J Lipid Res, 1995, 36(8): 1825–38.
Novotny JA; Zech LA; Furr HC; Dueker SR; Clifford AJ. Mathematical modeling in nutrition: Constructing a physiologic compartmental model of the dynamics of beta-carotene metabolism. Adv Food Nut Res, 1996, 40:25–54.
Parker RS; Swanson JE; Marmor B; Goodman KJ; Spielman AB; Brenna JT; Viereck; SM; Canfield WK. Study of beta-carotene metabolism in humans using 13C-beta-carotene and high precision isotope ratio mass spectrometry. Ann NY Acad Sci, 1993,691:86–95.
Pont F; Duvillard L; Maugeais C; Athias A; Persegol L; Gambert P; Verges B. Isotope ratio mass spectrometry, compared with conventional mass spectrometry in kinetic studies at low and high enrichment levels: Application to lipoprotein kinetics. Anal Biochem, 1997, 248, 277–87.
Rating D; Langhans CD. Breath tests: Concepts, applications and limitations. Eur J Pediatr, 1997, 156:S18–23.
Santhosh Kumar CR; Deutsch JC; Hassell KL; Kolhouse NM; Kolhouse JF. Quantitation of red blood cell folates by stable isotope dilution gas chromatography-mass spectrometry utilizing a folate internal standard. Anal Biochem, 1995, 10, 225 (1): 1–9.
Sears FW; Zemansky, MW; Young, HD. University Physics. 6th Ed. Addison-Wesley Pub. Co: Reading, Mass. 1982.
Tobias HJ; Brenna JT. High-precision D/H measurement from organic mixtures by gas chromatography continuous-flow isotope ratio mass spectrometry using a palladium filter. Anal Chem, 1996, 68(17):3002–3007.
Uphaus RA; Flaumenhaft E; Katz JJ. Isotope biology of 13C. Extensive incorporation of highly enriched 13C in the alga Chlorella vulgaris. Biochem Biophys Acta, 1970, 215:421.
Watson JT Introduction to Mass Spectrometry, 3rd Ed. Lippincott-Raven: Philadelphia. 1997.
Wolfe RR. Radioactive and Stable Isotope Tracers in Bio-Medicine-Principles and Practice of Kinetic Analysis. John Wiley and Sons: New York. 1992.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Dueker, S.R., Jones, A.D., Clifford, A.J. (1998). Protocol Development for Biological Tracer Studies. In: Clifford, A.J., Müller, HG. (eds) Mathematical Modeling in Experimental Nutrition. Advances in Experimental Medicine and Biology, vol 445. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1959-5_23
Download citation
DOI: https://doi.org/10.1007/978-1-4899-1959-5_23
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4899-1961-8
Online ISBN: 978-1-4899-1959-5
eBook Packages: Springer Book Archive