RESUMO
A mass spectrometry based method for the simultaneous determination of an in vivo Greenford-Ware or 'GW cocktail' of CYP450 probe substrates and their metabolites in both human plasma and urine is described. The probe substrates, caffeine, diclofenac, mephenytoin, debrisoquine, chlorzoxazone and midazolam, together with their respective metabolites and stable isotope labelled internal standards, are simultaneously extracted from the biological matrix using solid phase extraction in 96-well microtitre plate format, automated by means of a custom built Zymark robotic system. The extracts are analysed by fast gradient high performance liquid chromatography (HPLC) with detection by tandem mass spectrometry (MS/MS) using thermally and pneumatically assisted electrospray ionisation in both positive and negative ion modes and selected reaction monitoring. The methods are specific, accurate and precise with intra- and inter-assay precision (%CV) of less than 15% for all analytes.
Assuntos
Cafeína/sangue , Clorzoxazona/sangue , Sistema Enzimático do Citocromo P-450/metabolismo , Debrisoquina/sangue , Diclofenaco/sangue , Midazolam/sangue , Teofilina/sangue , Automação , Cafeína/análogos & derivados , Cafeína/farmacocinética , Cafeína/urina , Clorzoxazona/análogos & derivados , Clorzoxazona/farmacocinética , Clorzoxazona/urina , Cromatografia Gasosa/métodos , Cromatografia Líquida de Alta Pressão/métodos , Debrisoquina/análogos & derivados , Debrisoquina/farmacocinética , Debrisoquina/urina , Diclofenaco/análogos & derivados , Diclofenaco/farmacocinética , Diclofenaco/urina , Glucuronidase , Humanos , Indicadores e Reagentes , Midazolam/análogos & derivados , Midazolam/farmacocinética , Midazolam/urina , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Especificidade por Substrato , Teofilina/farmacocinética , Teofilina/urinaRESUMO
The identification of metabolites from the pyridylglutarimide 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione (PG, Rogletimide) was achieved using liquid chromatography-mass spectrometry with a thermospray interface (LC-TSP-MS). The urinary metabolites include PG N-oxide, the products of 4- and 5-hydroxylation in the piperidine residue (4- and 5-hydroxy-PG) and a gamma-butyrolactone derived via terminal hydroxylation in the ethyl residue. In addition to the above metabolites, several products of glutarimide ring-opening could be detected in the plasma extracts after multiple-dose treatment. Thus LC-TSP-MS is potentially a simple and rapid technique in studies of drug metabolism for the important glutarimide class of drug.
Assuntos
Aminoglutetimida/análogos & derivados , Antineoplásicos/metabolismo , Aminoglutetimida/sangue , Aminoglutetimida/metabolismo , Aminoglutetimida/uso terapêutico , Aminoglutetimida/urina , Antineoplásicos/sangue , Antineoplásicos/uso terapêutico , Antineoplásicos/urina , Neoplasias da Mama/tratamento farmacológico , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Padrões de ReferênciaRESUMO
This paper reports on the first national survey of adults concerning a history of childhood sexual abuse. Victimization was reported by 27% of the women and 16% of the men. Higher rates of abuse were found among men who grew up in unhappy families, lived for some period with only their mothers, who were currently residing in the West and who came from English or Scandinavian heritage. Higher rates of abuse were found among women who grew up in unhappy families, lived for some period without one of their natural parents, received inadequate sex education, were currently residing in the West or who were born after 1925.