RESUMEN
The metabolomics of urinary steroids was studied by gas chromatography-mass spectrometry in 25 patients with Cushing's syndrome without malignant potential and in 12 patients with malignant potential of adrenal neoplasms (Weiss score 1-3). Patients with adrenocortical adenoma (N=24) constituted the control group. In patients with Cushing's syndrome and malignant potential, increased urinary excretion of 16-oxo-androstendiol, tetrahydro-11-deoxycortisol, and 16-hydroxypregnendiol, which had 100% specificity and sensitivity >90% for the diagnosis of malignant potential. Additionally, non-classical 5-ene-pregnenes (16-OHpregnenolone, 21-OH-pregnenolone, 3ß,16,20-pregnentriol, and 3ß,17,20-pregnentriol) were identified. The revealed changes in the metabolomics of steroids can be early signs of malignant potential in patients with Cushing's syndrome. In patients with malignant potential, three signs of reduced activity of 11ß-hydroxysteroid dehydrogenase type 2 were detected and in patients without malignant potential, one sign was found. In patients with and without malignant potential, three signs increased activity of 5ß-reductase were found.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico , Adenoma Corticosuprarrenal/diagnóstico , Biomarcadores de Tumor/orina , Síndrome de Cushing/diagnóstico , Metabolómica/métodos , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/orina , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/orina , Adenoma Corticosuprarrenal/complicaciones , Adenoma Corticosuprarrenal/patología , Adenoma Corticosuprarrenal/orina , Adulto , Androstenodioles/orina , Cortodoxona/análogos & derivados , Cortodoxona/orina , Síndrome de Cushing/complicaciones , Síndrome de Cushing/patología , Síndrome de Cushing/orina , Detección Precoz del Cáncer , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Oxidorreductasas/orina , Pregnenodionas/orina , Pregnenos/orina , Pregnenolona/orinaRESUMEN
Restricted-access materials based on non-ionic surfactant-coated dodecyl-functionalized magnetic nanoparticles were prepared and applied to extract steroid hormones from environmental and biological samples. The magnetic nanoparticles were synthesized by co-precipitation, and were functionalized with dodecyltriethoxysilane, giving dodecyl-grafted magnetic nanoparticles (C12-Fe3O4). They were further modified with different non-ionic surfactants by self-assembly adsorption. Several types of non-ionic surfactants, Tween-20, 40, 60 and 85, and Span-40, 60 and 80, were investigated as the coatings. Tween surfactants coated C12-Fe3O4, named as TW-20 (40, 60, 85)-C12, exhibited good dispersibility in aqueous solution, which was a preferred character in extraction; besides, TW-20-C12 and TW-40-C12 showed good anti-interference ability and satisfactory reproducibility when they were used as magnetic solid-phase extraction (MSPE) sorbents. The factors that may influence the extraction, including the amount of magnetic nanoparticles, extraction and desorption time, the amount of salt addition, the type and volume of desorption solvent, the volume of methanol addition and pH of sample solution, were investigated in detail. High performance liquid chromatography-UV detection was employed for analysis of target analytes (steroid hormone compounds). The developed method was successfully used for the determination of the target analytes in environmental and urine samples. Both tested materials afforded good recovery, satisfactory reproducibility and low limits of detection for environmental samples, which indicates that the materials possessed anti-interference ability. However, compared to TW-40-C12, TW-20-C12 nanoparticles provided better recovery in relatively complex biological samples, which may indicate that the latter one is more appreciated in complex samples.
Asunto(s)
Androstenos/aislamiento & purificación , Contaminantes Ambientales/aislamiento & purificación , Nanopartículas de Magnetita/química , Pregnenodionas/aislamiento & purificación , Ríos/química , Extracción en Fase Sólida/métodos , Adsorción , Androstenos/análisis , Androstenos/orina , Cromatografía Líquida de Alta Presión , Contaminantes Ambientales/análisis , Contaminantes Ambientales/orina , Femenino , Humanos , Límite de Detección , Masculino , Metanol/química , Polisorbatos/química , Pregnenodionas/análisis , Pregnenodionas/orina , Reproducibilidad de los Resultados , Cloruro de Sodio/química , Tensoactivos/químicaRESUMEN
The pharmacokinetics, metabolism, and excretion of ciclesonide, a novel and effective inhaled glucocorticoid for the treatment of asthma, were investigated after intravenous and oral administration of 14C-ciclesonide in the mouse, rat, rabbit, and dog. The pharmacokinetics of ciclesonide in all animal species were characterized by a low oral bioavailability (approximately 6% or less), a high clearance, and a large volume of distribution. The apparent terminal half-life of ciclesonide was short; the apparent terminal half-life of the active desisobutyryl-ciclesonide metabolite (des-CIC or M1) was longer and ranged from 2.4 to 6.9 hours in the 4 species. Metabolites derived from ciclesonide in serum (or plasma) and excreta samples from the 4 animal species were profiled and identified by LC/RAM/MS (liquid chromatography/radioactivity monitor/mass spectrometry). Ciclesonide was extensively metabolized to yield des-CIC, which was further metabolized to primarily yield hippuric acid and hydroxylated metabolites, namely, isomers of cyclohexane-monohydroxylated des-CIC and B-ring-monohydroxylated des-CIC. Greater than 90% of intravenous and oral 14C-ciclesonide doses were recovered in all species; the main elimination route was fecal/biliary. A comparison of in vitro and in vivo metabolite profiles between mice, rats, rabbits, and dogs with those from humans indicated that metabolic pathways for ciclesonide were qualitatively similar in humans and in the 4 animal species.
Asunto(s)
Antiasmáticos/farmacocinética , Pregnenodionas/farmacocinética , Administración Oral , Animales , Antiasmáticos/administración & dosificación , Antiasmáticos/sangre , Antiasmáticos/orina , Área Bajo la Curva , Disponibilidad Biológica , Biotransformación , Cromatografía Liquida , Perros , Heces/química , Femenino , Semivida , Humanos , Inyecciones Intravenosas , Masculino , Tasa de Depuración Metabólica , Ratones , Pregnenodionas/administración & dosificación , Pregnenodionas/sangre , Pregnenodionas/orina , Conejos , Ratas , Ratas Wistar , Espectrometría de Masas en TándemRESUMEN
1. The structure of a previously reported but uncharacterized major metabolite of deflazacort in man, designated V, has been characterized by nmr, MS and IR spectral techniques. 2. The major changes in V relative to deflazacort are deacetylation to form the 21-alcohol and A-ring modification to the 1,2-epoxy-3-hydroxy analogue. 3. Based on the spectral data and comparison with model compounds the structure, including relative stereochemistry, is (1 beta, 2 beta, 3 beta, 11 beta, 16 beta,)-1,2-epoxy-3,11,21-trihydroxy-2'-methyl-5H'-pregn-4-4-eno [17,16-d]oxazol-20-one.
Asunto(s)
Antiinflamatorios/orina , Pregnenodionas/orina , Acetilación , Administración Oral , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Conformación Molecular , Estructura Molecular , Espectrofotometría InfrarrojaRESUMEN
Two HPLC methods for the separation of a mixture of corticoids including the oxazolinic corticoid deflazacort and its metabolite 21-hydroxydeflazacort using different water-tetrahydrofuran mobile phases were developed. Both separations allowed the detection and determination of fifteen out of sixteen corticoids using different C18 columns. Extraction data for deflazacort and its metabolite using different extraction procedures are also reported. These separation conditions were applied to urine samples from two male volunteers administered Dezacor, with both doping control and clinical purposes.
Asunto(s)
Antiinflamatorios/orina , Cromatografía Líquida de Alta Presión/métodos , Pregnenodionas/orina , Corticoesteroides/aislamiento & purificación , Corticoesteroides/orina , Adulto , Cromatografía Líquida de Alta Presión/estadística & datos numéricos , Cortisona/orina , Furanos , Humanos , Hidrocortisona/orina , Masculino , Estructura Molecular , Pregnenodionas/farmacocinética , Control de Calidad , Sensibilidad y Especificidad , Espectrofotometría Ultravioleta , AguaAsunto(s)
Pregnenodionas/metabolismo , Administración Oral , Animales , Disponibilidad Biológica , Proteínas Sanguíneas/metabolismo , Fenómenos Químicos , Química , Perros , Heces/metabolismo , Humanos , Cinética , Macaca fascicularis , Masculino , Pregnenodionas/administración & dosificación , Pregnenodionas/sangre , Pregnenodionas/orina , Unión Proteica , Ratas , Ratas Endogámicas , Especificidad de la Especie , Distribución TisularRESUMEN
A 17 year old female patient with hypertension, amenorrhoea and hirsutism was found to have subnormal levels of plasma and urinary cortisol, significant plasma levels of Reichstein's compound S and 21-deoxycortisol, high urinary levels of THS and pregnanetriolone as well as elevated levels of plasma and urinary testosterone. Treatment with 0.5 mg/day of dexamethasone or 25 mg/day cortisone reduced her hypertension and restored her menstrual cycles, but also resulted in the development of moon face, body striae and a gain in weight. Lower doses of cortisone were without effect. The deficient cortisol production coupled with the presence of unusual intermediates such as Reichstein's compound S and 21-deoxycortisol can be explained by a shift in the substrate specificity of 11beta-hydroxylase from C-21-hydroxylated substrates (i.e. compound S) to C-21-deoxy substrates (i.e. 17-hydroxyprogesterone).
Asunto(s)
Hiperplasia Suprarrenal Congénita/metabolismo , Hipertensión/metabolismo , Esteroide Hidroxilasas/deficiencia , 17-Cetosteroides/metabolismo , Adolescente , Amenorrea/metabolismo , Corticosterona/metabolismo , Femenino , Hirsutismo/metabolismo , Humanos , Hidrocortisona/metabolismo , Hidroxiprogesteronas/metabolismo , Pregnanotriol/metabolismo , Pregnenodionas/orina , Síndrome , Testosterona/orina , Tirotropina/orina , Transcortina/sangreRESUMEN
Computerised gas chromatography-mass spectrometry was employed in the identification of polar corticosteroid metabolites excreted in the urine from the macaque monkey (Macaca fascicularis) and the baboon (Papio hamadryas). The following steroids were identified in significant amounts in the urine from both species: 3alpha,17alpha,20alpha, 21-tetrahydroxy-5beta-pregnan-11-one; 3alpha,17alpha,20beta,21-tetrahydroxy-5beta-pregnan-11-one; 5beta-pregnane-3alpha,11beta,17alpha,20alpha,21-pentol; 5beta-pregnane-3alpha,11beta,17alpha,20beta-pentol; 5alpha-pregnane-3beta,11beta,17alpha,20beta,21-pentol. 11beta,17alpha,21-Trihydroxy-4-pregnene-3,20-dione (cortisol), 11beta,17alpha,20beta,21-tetrahydroxy-4-pregnen-3-one and 11beta,17alpha,20beta,21-tetrahydroxy-5xi-pregnan-3-one were identified in macaque monkey urine. Two steroids, 17alpha,20beta,21-trihydroxy-4-pregnane-3,11-dione and 17alpha,20alpha,21-trihydroxy-4-pregnene-3,11-dione were excreted as major C21 metabolites in the baboon but were not identified in the urine from the macaque monkey. 3beta-Hydroxy-5alpha-pregnane metabolites were identified in the urine from both species. All these steroids were excreted conjugated to glucuronic acid, evidenced by their recovery after hydrolysis with beta-glucuronidase enzyme. An efficient 20beta-reduction of corticosteroids in both species is apparent, and the excretion pattern of polar steroid metabolites in the two species was shown to be similar.