Urinary isotopic ratios

Miller et 1988 n = 12 adolescents S. n = 6 n = 6 Age 10-17 years Treatments in randomized order with 3-week washout period 1. 250-mg elemental Ca as CaCOs (enriched with Ca) Compare CaAbs for CCM versus CaCOa using dual isotope mettiod using a crossover design and measured urinary isotope ratio after 24 h Mean FxAbs SEM results 1. CCM 36.2 2.7% (range 27.3-53.3%) 2. CaC03 26.4 2J2% (range 12.8-39.6%) Ctest for FxAbs difference CCM > CaCOa (p <. 03)... 

To develop a method to determine urinary biomarkers for benzoates. The method involves the use of gas chromatography-combustion-isotope ratio mass spectrometry. It is proposed that the procedure developed will allow differentiation of natural benzoates from synthetic ones. 

Results of isotope ratio measurements from an earlier study that used a similar protocol to the one just described are shown in Figure 3. These curves show plasma Isotope levels for both the i.v.oral tracer, labelled as PTA and CTA respectively. It is generally accepted that isotopic enrichment, atom percent excess, of urine reflects that of plasma, and after the initial period of rapid mixing, urinary atom percent excess is used in lieu of plasma measurements. The curves drawn through the data are those generated using the proposed model for calcium kinetics. 

True fractional absorption can be determined from urinary Isotope measurements by estimating the ratio SA SAj where Sa is... 

Aguilera R, Becchi M, Casablanca H> Hatton CK, Gatlin DH, Starcevic B, et al. Improved method of detection of testosterone abuse by gas chromatography/combustion/isotope ratio mass spectrometry analysis of urinary steroids. J Mass Spectrom 1996 31 169-76. 

Cawley and Flenker [175] provide an overview of the application of IRMS to doping control. The authors discuss the benefits of measuring carbon isotope ratios of urinary steroids to confirm their synthetic origin based on the carbon isotope ratio content. The authors also address some of the issues that can be encountered in such analyses and the importance of caution when interpreting the data. 

Phillips, A. (1999) Gas chromatography combustion isotope ratio mass spectrometry for confirming testosterone administration from urinary androstanediols. Micromass Application Note 501. 

Shackleton, C.H.L., Phillips, A., Chang, T., Li, Y. (1997) Confirming testosterone administration by isotope ratio mass spectrometric analysis of urinary androstanediols. Steroids, 62,379-387. 

Becchi, M., Aguilera, R., Farizon, Y. (1994) Gas chromatography/ combustion/isotope-ratio mass spectrometry analysis of urinary steroids to detect misuse of testosterone in sport. Rapid Communications in Mass Spectrometry, 8,304-308. 

Miller et al., 1989 n = 6 children n = 3 n — 3 Age range 11-17 years 250 mg Ca as CCM enriched with tracer in form of chewable tablets Stable dual isotope tracers used to quantify CaAbs in urine and serum. Comparison of CCM chewable versus CCM swallowable supplements and CaCOa from data collected previously in same subjects Based on urinary excretion which correlated with serum data (r = 0.85) x SD% CaAbs from chewable CCM for molar ratio 6 2 3 (41.4 8.2%) > swallowable CCM for molar ratio 5 1 1 (39.5 10.6%) > CaCOa (26.7 7.8%) Chewable CCM > CaCOa (p =. 047) and swallowable CCM > CaCO (p =. 094)... 

Androsterone and 5)3-androsterone, which are the major metabolites, were thought to be uniquely derived from the plasma androstenedione pool. Korenman et al. [170,388] demonstrated by the double isotope tracer method using carbon-14-labeled testosterone and tritium-labeled androstenedione that neither androsterone nor 5 -androsterone is a unique metabolite of a plasma androstenedione pool. A unique steroid metabolite has been defined by Dorfman [326] as a steroid persisting or formed during metabolism which can be related to one and only one tissue steroid. Korenman et al. obtained different tritium/carbon-14 ratios for androsterone and 5/3-androsterone, suggesting that other pathways of testosterone and androstenedione metabolism also exist. These other pathways, possibly metabolism of testosterone and androstenedione by peripheral tissue, may be responsible for the relative enrichment of either the 5a- or the 5/8-isomer of the urinary metabolites [305]. 

Sensitivity is closely related to the specificity and precision of a method. As an extremely important aspect of any method for plasma steroids, and of many for urinary steroids, it has been much discussed. In terms of the best levels of signal-to-noise ratio obtained with pure substances under ideal conditions, the mass spectrometer attached directly to a good GLC column is probably the most sensitive analytical method currently available. In terms of steroids in natural sources the most sensitive methods at present established are those using the isotopic-displacement (protein-binding) technique (0.1-0.5 ng) and electron-... 

From metabolic studies, an isotopic caffeine breath test has been developed that detects impaired liver function using the quantitative formation of labeled carbon dioxide as an index. From the urinary excretion of an acetylated uracil metabolite, human acet-ylator phenotype can be easily identified and the analysis of the ratio of the urinary concentrations of other metabolites represents a sensitive test to determine the hepatic enzymatic activities of xanthine oxidase and microsomal 3-methyl demethylation, 7-methyl demethylation, and 8-hydroxylation. Quantitative analyses of paraxanthine urinary metabolites may be used as a biomarker of caffeine intake. Fecal excretion is a minor elimination route, with recovery of only 2-5% of the ingested dose. 

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