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At least 19 recordsLinked to original sources
PubMed2005

Direct determination of the ratio of tetrahydrocortisol+allo-tetrahydrocortisol to tetrahydrocortisone in urine by LC-MS-MS.

The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) is responsible for the interconversion of both the hormonally inactive cortisone and the active cortisol. This enzyme activity, which has implications in the pathogenesis of numerous diseases, is reflected in the ratio of tetrahydrometabolites of cortisol (allo-tetrahydrocortisol and tetrahydrocortisol) to those of cortisone (tetrahydrocortisone). Several methods have been proposed in the literature to determine such a ratio in urine. Most of them require tedious and extensive extraction and derivatization steps and make use of gas-chromatographic techniques, including gas chromatography coupled to mass spectrometry (GC-MS). We present here an alternative approach for the direct determination of such a ratio in urine by using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS), based on a minimal sample treatment. Actually, the limit of detections (LODs) for pure standards in water permitted a simple dilution of the urine samples prior to the analysis, hence, an accurate optimization of the high performance liquid chromatography (HPLC) separation was needed in order to get rid of the severe influence of the urine matrix on the ionization efficiency. Besides, the nature of some interfering species was deeply investigated, as well as the suitability of some commercial deuterated steroids as internal standards. All these led to the final method, which was based on a HPLC separation on a C8 column and a ternary gradient water/methanol/acetonitrile. In parallel, an appropriate sample preparation was set up, which consisted of an enzymatic hydrolysis of the conjugated species and a followed 1:20 dilution. Preliminary measurements on real urine samples were performed as well.

Calibration↗
PubMed1999

Synthesis of deuterium-labeled tetrahydrocortisol and tetrahydrocortisone for study of cortisol metabolism in humans.

A method is described for the preparation of multi-labeled tetrahydrocortisol (3alpha,11beta,17alpha,21-tetrahydroxy-5beta-[1, 2,3,4,5-2H5]pregnan-20-one, THF-d5), allo-tetrahydrocortisol (3alpha,11beta,17alpha,21-tetrahydroxy-5alpha-[1 ,2,3,4,5-2H5]pregnan-20-one, allo-THF-d5), and tetrahydrocortisone (3alpha,17alpha,21-trihydroxy-5beta-[1,2,3,4,5-2H5]pre gnane-11,20-dione, THE-d5) containing five non-exchangeable deuterium atoms in the steroid ring A. Reductive deuteration at C-1, C-2, C-3, C-4, and C-5 of prednisolone or prednisone was performed in CH3COOD with rhodium (5%) on alumina under the deuterium atmosphere. The isotopic purities of the labeled compounds as [2H5]-form were estimated to be 86.17 atom%D for THF-d5, 74.46 atom%D for allo-THF-d5 and 81.90 atom%D for THE-d5, based on the ion intensities in the region of the molecular ion of methoxime-trimethylsilyl (MO-TMS) derivatives measured by GC-MS.

Chromatography, Liquid↗
PubMed1998

Simultaneous determination of tetrahydrocortisol and tetrahydrocortisone in human plasma and urine by stable isotope dilution mass spectrometry.

A capillary gas chromatographic-mass spectrometric method for the simultaneous determination of tetrahydrocortisol (THF, 3alpha,11beta,17alpha,21-tetrahydroxy-5beta-preg nane-20-one), allo-tetrahydrocortisol (allo-THF, 3alpha,11beta,17alpha,21-tetrahydroxy-5alpha-pre gnane-20-one) and tetrahydrocortisone (THE, 3alpha,17alpha,21-trihydroxy-5beta-pregnane-11,20-dion e) in human plasma and urine is described. [1,2,3,4,5-2H5]THF (THF-d5), allo-[1,2,3,4,5-2H5]THF (allo-THF-d5) and [1,2,3,4,5-2H5]THE (THE-d5) were used as internal standards. A double derivatization (bismethylenedioxypentafluoropropionate, BMD-PFP) made possible the separation of the three tetrahydrocorticoids with good gas chromatographic behavior. Quantitation was carried out by selected-ion monitoring of the characteristic fragment ions ([M-30]+) of the BMD-PFP derivatives of THF, allo-THF and THE. The sensitivity, specificity, precision and accuracy of the method were demonstrated to be satisfactory for measuring low concentrations of THF, allo-THF and THE in human plasma and urine.

Deuterium↗
PubMed2006

Determination of free tetrahydrocortisol and tetrahydrocortisone ratio in urine by liquid chromatography-tandem mass spectrometry.

OBJECTIVE: Measurement of urinary free tetrahydrocortisol and tetrahydrocortisone ratio (allo-THF+THF)/THE is clinically important in the diagnosis of hypertension caused by congenital absence of 11beta-hydroxysteroid dehydrogenase type 2 (apparent mineralocorticoid excess, AME) or inhibition of the enzyme after licorice ingestion. Although gas chromatography-mass spectrometry (GC-MS) provides reliable results, it requires derivatization and is lengthy and time-consuming. The purpose of this study was to demonstrate that detection by liquid chromatography-mass spectrometry (LC-MS) is a potentially superior method. MATERIAL AND METHODS: The analysis utilizes 1 mL urine. The samples were extracted with solid-phase extraction (SPE) using ethyl acetate as eluent. The extract was evaporated to dryness, and allo-tetrahydrocortisol (allo-THF), THF and THE concentrations were analyzed by LC-MS/MS operating in the negative mode after separation on a reversed-phase column. The calibration curves exhibited consistent linearity and reproducibility in the range of 7.5-120 nmol/L. Interassay CVs were 7.0-10 % at mean ratios of (allo-THF+THF)/THE of 0.54-1.9. The detection limit of the analytes was 0.4-0.8 nmol/L (signal-to-noise ratio = 3). The mean recovery of the three analytes ranged from 88 to 95 %. The regression equation for the free ratio using the LC-MS/MS (x) method and the total ratio using the GC-MS (y) method was: y = 0.30x+0.91 (r = 0.61; n = 25). CONCLUSIONS: The sensitivity and specificity of the LC-MS/MS method offer an advantage over GC-MS by eliminating derivatization. The high costs of equipment are balanced by higher through-put, owing also to shorter chromatographic run times.

Chromatography, Liquid↗
PubMed2002

Role of ketoconazole treatment in urinary-free cortisol-to-cortisone and tetrahydrocortisol-to-tetrahydrocortisone ratios in nonectopic Cushing's syndrome.

We hypothesized that in nonectopic Cushing syndrome there is an insufficient activity of type II (renal) 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) that is related to cortisol excess, rather than to corticotropin (adrenocorticotropic hormone [ACTH]) levels. We measured plasma ACTH and urinary-free cortisol (UFF), urinary-free cortisone (UFE), tetrahydrocortisol (UTHF), and tetrahydrocortisone (UTHE) in 24-h urine samples of 24 healthy subjects and 15 patients diagnosed with nonectopic Cushing syndrome. Then, in the group of patients, a new 24-h urine sample was collected after treatment with 800 mg daily of ketoconazole. The UFF/UFE and UTHF/UTHE ratios were calculated as an estimation of 11beta-HSD2 activity. The patients had an increase in both the UFF/UFE (19.95 +/- 10.3 vs 5.78 +/- 4.72 nmol/24 h; p < 0.0001) and UTHF/UTHE ratios (5.36 +/- 5.23 vs 1.39 +/- 0.95 nmol/24 h; p < 0.001). Both UFF/UFE and UTHF/UTHE ratios decreased after ketoconazole treatment (19.95 +/- 10.3 vs 12.2 +/- 6.9 nmol/24 h; p < 0.005; and 5.36 +/- 5.23 vs 1.62 vs 1.21 nmol/24 h; p < 0.001, respectively). The control subjects had a significant relationship between UFF and UFE (r = 0.70, p < 0.0001), and between UTHF and UTHE (r = 0.75, p < 0.0001) that did not exist in the patient group. After ketoconazole treatment, the decrease in cortisol excretion in the patient group allowed a positive and significant relation between UFF and UFE (r = 0.64, p < 0.01) and between UTHF and UTHE (r = 0.56, p < 0.05) to appear. There was not any significant relationship between either UFF/UFE or UTHF/UTHE ratios and plasma levels of ACTH.

Adult↗
PubMed1980

Urinary tetrahydrocortisone and tetrahydrocortisol glucosiduronates in normal newborns, children and adults.

Utilizing a simple, highly specific radioimmunoassay (RIA), we measured the excretion of the glucosiduronate conjugates of tetrahydrocortisone (THE-gluc) and tetrahydrocortisol (THF-gluc) in adults (n = 16), children (n = 58) and newborns (n = 5), in order to establish a normal range of values for age and surface area. Both tetrahydrometabolites showed a linear increase with age but became constant for all individuals except newborns when results were calculated per square meter. Newborns excreted disproportionately low levels of these metabolites for their size. In children of similar ages, when 24h urine collections (n = 13) were compared to spot AM specimens (AM-Sp) (n = 45) in which the daily volume was estimated by creatinine excretion, THE-gluc/m2 levels were significantly higher in AM-Sp urines but THF-gluc/m2 levels were similar. Levels of both metabolites were markedly elevated in two patients with hyperadrenal states and low in three patients with hypoadrenal states compared to normal values per m2. These results indicate that the RIA for THE-gluc and THF-gluc can be a useful indirect test of cortisol secretion in children as well as in adults. Although 24h urine collections are more accurate, creatinine corrected AM-Sp urines may be clinically useful when values of these metabolites per m2 are compared to appropriate controls.

Adolescent↗
PubMed1977

Studies in the biotransformation of cortisol to the cortoic acids in man. II. The central role of tetrahydrocortisol and tetrahydrocortisone as intermediates.

The possible role of THF and THE as intermediates in the biotransformation of cortisol to the cortoic acids was studied by giving 3H-THF + 14C-cortisol tracers and 3H-THE + 14C cortisol tracers to two subjects each, measuring the 3H/14C isotope ratios of the urinary cortoic acid metabolites and relating these ratios to the dose ratio. Isotope ratios substantially higher than the dose ratio indicate that the tetrahydro compound is a better precursor than cortisol, and isotope ratios that are essentially identical to that of urinary THF or THE, respectively, indicate that the tetrahydro compound may be an obligatory intermediate in the cortisol leads to cortoic acids pathway. The isotope ratio data in these studies clearly establish that THF was a preferential precurosor of the 11 beta-hydroxy cortoic acids (cortolic and beta-cortolic) and THE was a preferential precursor of the 11-ketone cortoic acids (cortolonic and beta-cortolonic). Furthermore, the data strongly suggest that THF and THE may be obligatory intermediates in cortoic acid formation.

Carboxylic Acids↗
PubMed1977

The use of tetrahydrocortisone-3-beta-D-glucuronide in the measurement of urinary 17-hydroxycorticosteroids.

THE 3-G was added to H2O and 56 urines, and the recovered THE was measured by the Porter-Silber method. The recovery from H2O was quantitative (98 +/- 2%), but highly variables from urine, ranging from 35 to 100%. The necessity of the proper standard in analysis of urinary steroid glucuronides was demonstrated. The presence in urine of endogenous inhibitors to beta-glucuronidase was confirmed.

17-Hydroxycorticosteroids↗