Urine ratio of tetrahydrocortisol to tetrahydrodeoxycortisol to screen for the systemic administration of cortisone and hydrocortisone.
We use gas chromatography-mass spectrometry (GC-MS) to determine the urine peak area ratio of tetrahydrocortisol (THF) to tetrahydrodeoxycortisol (THS) in spot urine samples of eight male volunteers after a single intramuscular injection of 100 mg hydrocortisone (HC) and after a single oral administration of 10 mg HC at six different post-treatment times over 24 h with 1 week between the two treatments. Control spot urine samples were also obtained from a group of 100 volunteers of each sex for GC-MS analysis. In addition, one female volunteer was collected for GC-MS and isotope ratio mass spectrometry (IRMS) analysis after a single oral administration of 40 mg HC and 40 mg cortisone (C) at 15 and 10 different post-treatment times over 30 h, respectively. IRMS analysis focused on the acetylated derivative of 11-keto-etiocholanolone (11KE) and 11beta-hydroxy-etiocholanolone (11OHE) as target metabolites, and on androsterone (A) as an endogenous reference compound (ERC) for calculating the corresponding delta(13)C (per thousand) depletion values. There was a small but significant sex-related difference for the THF/THS ratio in the control group with mean THF/THS ratio values of 10 and 13.5 for women and men, respectively. A cut-off value of 28 (mean+2 S.D.) for the THF/THS ratio offered a narrow detection window with 39% of suspicious samples after HC-oral treatment, and a wide detection window with 94% of suspicious samples after HC-intramuscular administration in men. For the woman the same cut-off value offered a wide detection window after HC and C administration with 100% and 90% of suspicious samples, respectively. On the basis of a cut-off value of 3 per thousand for the delta(13)C (per thousand) depletion, the exogenous origin was widely evidenced for at least one target compound in 93% and 80% of the HC and C samples, respectively. We conclude by discussing the predictive ability of the urine THF/THS ratio and its usefulness in pointing out suspicious samples resulting from the systemic administration of HC and C.
Meklat
Noura
N
Département des Analyses, AFLD, 92290 Châtenay-Malabry, France.
Tabet
Jean-Claude
JC
de Ceaurriz
Jacques
J
D000284:Administration, Oral; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D016022:Case-Control Studies; D003348:Cortisone / Q000008:administration & dosage* / Q000737:chemistry; D003350:Cortodoxone / Q000031:analogs & derivatives* / Q000652:urine; D004300:Doping in Sports; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000737:chemistry; D007273:Injections, Intramuscular; D008297:Male; D012737:Sex Factors; D015813:Substance Abuse Detection / Q000379:methods*; D013760:Tetrahydrocortisol / Q000652:urine*
D000893:Anti-Inflammatory Agents; C009412:tetrahydro-11-deoxycortisol; D013760:Tetrahydrocortisol; D003348:Cortisone; D003350:Cortodoxone; D006854:Hydrocortisone