RESUMO
A method for the detection and identification of penbutolol and its metabolites in human body fluid by using gas chromatography-mass spectrometry was established. The urine was extracted with diethyl ether-isopropanol and the plasma was extracted with Sep-Pak column. After TMS derivatization the sample was analyzed with GC-MSD. Six metabolites of penbutolol were found in urine sample. The recovery was 90.83% for urine and 85.88% for plasma. The detection limit of penbutolol was 5 pg.
Assuntos
Antagonistas Adrenérgicos beta/metabolismo , Pembutolol/metabolismo , Antagonistas Adrenérgicos beta/urina , Adulto , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Pembutolol/urinaRESUMO
The metabolites of 1-tert.-butylamino-3-(2-cyclopentylphenoxy)propan-2-ol (penbutolol, Betapressin), penbutolol 2-glucuronide, 4'-OH-penbutolol 2-glucuronide, 4'-OH-penbutolol 4-sulfate and 1"-dehydropenbutolol 2-glucuronide were determined in urine by high-performance liquid chromatography (HPLC). The compounds were determined after direct injection, that is to say without prior cleavage of the conjugates to the corresponding aglycones. In the case of the glucuronides, the urine was injected into the HPLC system without further sample preparation. The sulfate was determined after ion-pair extraction. Fluorimetric detection was employed. Depending on the compound, the detection limits lay between 0.07 and 0.3 micrograms/ml. This method was used to determine the cumulative urinary excretion of a subject.
Assuntos
Pembutolol/urina , Propanolaminas/urina , Adulto , Fenômenos Químicos , Química , Cromatografia Líquida de Alta Pressão , Humanos , Masculino , Pessoa de Meia-Idade , Pembutolol/análogos & derivados , Pembutolol/farmacocinéticaRESUMO
In the present paper physico-chemical and analytical studies on penbutolol sulfate (Hoe 893d) are reported. In addition to an interpretation of ultraviolet and fluorometric spectra, data are given regarding the dissociation constant, solubility, distribution, and protein binding. The substance and its major metabolte, as well as their glucuronides, are detectable by means of a selective fluormetric method. Moreover, mention is made of the results of a human pharmacokinetic study.
Assuntos
Pembutolol/análise , Propanolaminas/análise , Proteínas Sanguíneas/metabolismo , Fenômenos Químicos , Físico-Química , Humanos , Técnicas In Vitro , Pembutolol/sangue , Pembutolol/urina , Ligação Proteica , Solubilidade , Espectrometria de Fluorescência , Espectrofotometria UltravioletaRESUMO
The metabolites of 1-tert.-butylamino-3-(2-cyclopentylphenoxy)propan-2-ol (penbutolol Betapressin) penbutolol 2-glucuronide, 4'-OH-penbutolol 2-glucuronide, 4'-OH-penbutolol 4'-sulfate and 1''-dehydropenbutolol 2-glucuronide were isolated from the urine of patients, purified by high-performance liquid chromatography and characterised by 1H-NMR and mass spectroscopy. Penbutolol 2-glucuronide and 4'-OH-penbutolol 4'-glucuronide were synthesised in vitro from penbutolol and 4'-OH-penbutolol, respectively, using glucuronyltransferase.