Quantitative metabolic profiling of twelve tetrahydrocorticosteroid glucuronides in urine by isotope dilution LC-ESI-linear ion trap MS/MS

摘要

It is widely accepted that the adrenocortical steroids are extensively metabolized to tetrahydro-reduced derivatives and appear in urine largely as 3- and 21-monoglucuronide of tetrahydrocortisol (THF), tetrahydrocortisone (THE), tetrahydro-11-deoxycortisol (THS), and their 5alpha-stereoisomers. Therefore, a suitable analytical method is requested to measure all twelve tetrahydrocorticosteroid glucuronides (THC-Gs) in human urine in order to define corticosteroid metabolism and hypothalamic-pituitary-adrenal cortical axis activity. However, measurements of these glucuronides have been done indirectly using GC-MS or LC-MS after enzymatic deconjugation. In the present study, a direct method for simultaneous determination of twelve THC-Gs (Figure 1) in human urine by isotope dilution LC-ESI-linear ion trap MS/MS was developed, and the method was applied to quantitate THC-Gs in healthy volunteers as well as patients with excessive cortisol production [1].