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Titolo:
HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY FOR HUMAN LIVER MICROSOMAL OMEPRAZOLE METABOLISM
Autore:
ANDERSSON T; LAGERSTROM PO; MINERS JO; VERONESE ME; WEIDOLF L; BIRKETT DJ;
Indirizzi:
ASTRA HASSLE AB S-43183 MOLNDAL SWEDEN FLINDERS UNIV S AUSTRALIA,DEPT CLIN PHARMACOL BEDFORD PK SA 5042 AUSTRALIA
Titolo Testata:
Journal of chromatography. Biomedical applications
fascicolo: 2, volume: 619, anno: 1993,
pagine: 291 - 297
SICI:
0378-4347(1993)619:2<291:HLAFHL>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
RANITIDINE; PLASMA; URINE; SLOW;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
19
Recensione:
Indirizzi per estratti:
Citazione:
T. Andersson et al., "HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY FOR HUMAN LIVER MICROSOMAL OMEPRAZOLE METABOLISM", Journal of chromatography. Biomedical applications, 619(2), 1993, pp. 291-297

Abstract

Assays for the measurement of omeprazole metabolites in plasma and urine have been reported. but when applied to the determination of omeprazole metabolites formed by human liver microsomal incubations there were obvious limitations in sensitivity. The present high-performance liquid chromatographic (HPLC) assay, which comprises extraction, evaporation and reconstitution, several-fold more sensitive with a limit of detection of approximately 2 pmol (2 nM in incubate) for omeprazole sulphone and 25 pmol (25 nM in incubate) for hydroxyomeprazole. Extraction efficiency is essentially quantitative and is highly reproducible (coefficient of variation = 2.1 % for both metabolites). The assay is linear over a wide range of concentrations and the formation of the metabolites is linear with respect to both time (to 15 min) and protein concentration (to 1.5 mg/ml). Two minor metabolites, one of which was identified tentatively as 5-O-desmethylomeprazole, were also formed by human liver microsomes and could be determined by this method. Preliminary studies of the formation of omeprazole sulphone and hydroxyomeprazole showed that the formation kinetics in human liver microsomes werebiphasic for both metabolites, suggesting that at least two differentcytochrome P450 isoforms are involved in their formation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/06/20 alle ore 02:00:01