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Metabolic dissimilarity between (9,12,12‐ 2 H)cortisol and natural cortisol in vivo . Can deuterated cortisol be used for the measurement of the urinary cortisol production rate?
Author(s) -
Kraan G. P. B.,
Chapman T. E.,
Drayer N. M.,
Nagel G. T.,
Wolthers B. G.,
Colenbrander B.,
Fentenervan Vlissingen M.
Publication year - 1989
Publication title -
biomedical and environmental mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0887-6134
DOI - 10.1002/bms.1200180905
Subject(s) - chemistry , isotope dilution , urine , dilution , endocrinology , isotope , glucocorticoid , medicine , deuterium , metabolism , hydrocortisone , kinetic isotope effect , chromatography , in vivo , tritium , mass spectrometry , biochemistry , biology , physics , microbiology and biotechnology , quantum mechanics , thermodynamics , nuclear physics
The metabolism of deutrated cortisol (9,12,12,‐ 2 H)cortisol, ( 2 H 3 ‐F) was compared to that of radioactive cortisol ( 3 H 2 ‐F) and natural cortisol, when these three compounds were administered simultaneously to an adrenalectomized piglet. The relative isotope dilution of tritium was determined from the specific activities of the main urinary neutral cortisol metabolites, tetrahydrocortisone (THE) and tetrahydrocortisol (THF), normalized to that of the cortisol mixture administered. To obtain a comparison of the isotope dilution of deuterium in the metabolites THE and THF to that in the cortisol mixture, the three steroids were converted to the common oxidation product 11‐oxo‐aetiocholanolone, and deivatized to the methoxime‐ tert ‐butyl‐dimethylsilyl ether. The relative 2 H‐isotope dilution then was measured by gas chromatography/mass spectrometry. It was found that the specific activity of THE in the cumulative urine collections was similar to that of the cortisol mixture administered; the two‐day value was, however, less. The specific activity of THF was slightly but significantly smaller than 1 (∼0.9) at all times. The relative 2 H‐isotope dilution in THE was slightly but significantly larger than one (∼1.1) at all times, whereas that in the THF was larger than 1.0 at 9 and 32 h or equal to 1.0 at 20 and 47 h of urine collection. When comparing the metabolism of the two tracer cortisol species the quotient of the 3 H‐ and the 2 H‐isotope dilutions in THE and THF was smaller than 1.0. It can be concluded that ( 2 H 3 )cortisol may be used for the determination of the cortisol production rate.