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J Pharm Biomed Anal ; 48(1): 151-7, 2008 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-18571352

RESUMO

The non-selective beta-adrenergic receptor antagonist propranolol [1-(isopropylamino)-3-(1-naphthoxy)-2-propanol] is metabolised extensively in vivo. Enumerating and identifying the many metabolites that result from multiple biotransformations provides a considerable analytical challenge, greatly aided by efficient chromatography coupled to sensitive mass spectrometric detection. Here the use of the newly introduced high-resolution technique of "ultra performance liquid chromatography" (UPLC) linked to quadrupole time-of-flight mass spectrometry (TOFMS) with simultaneous [(14)C]-radioflow detection was applied to rapid metabolite profiling. [14C]-propranolol, dosed intraperitoneally to rat at 25 mg kg(-1) and 200 microCi kg(-1) was used as a model compound for this evaluation. Some 14 metabolites were detected in the urine by this technique including a number of conjugated metabolites such as sulphates, several isobaric glucuronides and two novel di-glucuronides.


Assuntos
Antagonistas Adrenérgicos beta/farmacocinética , Antagonistas Adrenérgicos beta/urina , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Propranolol/farmacocinética , Propranolol/urina , Antagonistas Adrenérgicos beta/análise , Animais , Biotransformação , Radioisótopos de Carbono/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Masculino , Estrutura Molecular , Propranolol/análise , Propranolol/química , Ratos , Ratos Wistar , Urinálise/métodos
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