Abstract
We have developed an isotope dilution method for determination of deoxycholic acid pool size and input rate which employs oral administration of 50 mg of [24-13C]deoxycholic acid and serum sampling. The method has been validated by classical isotope dilution technique using [24-14C]deoxycholic acid and bile sampling in five patients with colonic adenomas. Excellent agreement between pool sizes and input rates determined with 13C/12C isotope ratio measurements in serum and 14C measurements in bile was obtained when isotope ratios were measured in the conjugated fraction of deoxycholic acid in serum. We conclude that pool size and input rate of deoxycholic acid can accurately be determined by blood sampling after oral administration of [24-13C]deoxycholic acid, therewith eliminating the use of radioactive tracers and the need for bile sampling.
Highlights
Analytical methods isC/ipC isotope ratio measurements were carried out using combined capillary gas-liquid chromatographyelectron impact mass spectrometry and selected ion monitoring
The values for the fractional turnover rates and input rates obtained in conjugated deoxycholic acid (DCA) in serum and those obtained in biliary DCA using "C showed good agreement with the values calculated from specific activity measurements of "C in bile (Table 1).Pool sizes, fractional turnover rates, and input rates measured in conjugated DCA in serum of healthy volunteers averaged 10.5pmol*kg-', 0.32 d-I, and 3.5 pmol kg-', respectively
ISC/'*C isotope ratios in the conjugated fraction of DCA in serum can be measured with sufficient accuracy to obtain decay curvesof 1sC/12Cisotope ratios in human serum after oral administration of as little as 50 mg of ["CIDCA
Summary
Materials and instrumentation [24-13C]DCA was purchased from Merck Sharp & Dohme, Montreal, Canada (91% 'C as determined by capillary gas-liquid chromatography-mass spectrometry). All other materials and their preparations were the same as described recently (1l). Five female patients aged 41 to 65 years with colonic adenomas documented histologically were studied. Eight healthy volunteers aged 25 to 40 years (five males, three females) were studied. They were all clinical personnel and were not awareof any hepatobiliaryor gastrointestinal disease. The project was approved by the Medical Ethical Committee of the MunicipalHospital of Arnhem in 1983and informed consent was obtained from all patients and healthy volunteers
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