Simultaneous determinations of tolbutamide and its hydroxy and carboxy metabolites in serum and urine: application to pharmacokinetic studies of tolbutamide in the rat.
J Pharm Sci
; 78(10): 863-6, 1989 Oct.
Article
em En
| MEDLINE
| ID: mdl-2600795
ABSTRACT
Methods of analysis of tolbutamide (1) and its hydroxylated (2) and carboxylated (3) metabolites in serum and urine based on high-performance liquid chromatography were developed. The separation was performed on a Apex ODS column in the isocratic mode using a mobile phase composed of 22.5% acetonitrile, 77.5% Sorensen phosphate buffer (pH 7.0), and 0.30 mL of tetrabutylammonium phosphate reagent (Pic A). The compounds were detected at 254 mm. The retention times of 3, 2, 1, and the internal standard chlorpropamide were 3.1, 4.1, 14.8, and 10.0 min, respectively. These conditions were suitable for the simultaneous quantitation of 1, 2, and 3 in serum or plasma samples, but not for the determination of metabolites 2 and 3 in urine. For the analysis of 2 and 3 in urine, the mobile phase was modified to 18% acetonitrile, 82% Sorensen phosphate buffer (pH 7.0), and 0.35 mL of Pic A. Under these conditions, the retention times of the carboxy and hydroxylated metabolites and the internal standard salicylic acid were 4.6, 6.7, and 8.1 min, respectively. These methods were applied to study the pharmacokinetics of 1 administered intravenously and intraperitoneally to the rat. Tolbutamide was almost completely recovered as metabolites 2 and 3 in the urine within 24 h.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tolbutamida
Limite:
Animals
Idioma:
En
Revista:
J Pharm Sci
Ano de publicação:
1989
Tipo de documento:
Article