Quantitative determination of tolbutamide and its metabolites in human plasma and urine by high-performance liquid chromatography and UV detection.
An isocratic, high-performance liquid chromatography method has been developed for simultaneous determination of the oral antidiabetic tolbutamide and two of its metabolites, 4-hydroxytolbutamide and carboxytolbutamide, in human plasma and urine. The method was based on simple one-step liquid-liquid extraction with tertiary-butyl methyl ether as extraction solvent. The chromatographic eluent was 23:77 (v/v) methanol: 0.01 M aqueous sodium acetate buffer pH 3.0, and the UV detection was performed at a wavelength of 230 nm. The limit of detection was 0.1 microM for tolbutamide in plasma and 1.5 microM, 0.5 microM, and 0.75 microM for carboxytolbutamide, 4-hydroxytolbutamide, and tolbutamide, respectively, in urine. The limit of quantitation was 0.5 micro for tolbutamide in plasma and 2 microM, 0.75 microM, and 1.25 microM for carboxytolbutamide, 4-hydroxytolbutamide, and tolbutamide, respectively, in urine. The overall mean recoveries ranged from 91% to 109% for tolbutamide in plasma and from 80% to 98% in urine for all three compounds.
Hansen
L L
LL
Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense University.
Brøsen
K
K
D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007004:Hypoglycemic Agents / Q000032:analysis* / Q000097:blood / Q000652:urine; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D014044:Tolbutamide / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood / Q000652:urine; D000096926:Benzenesulfonamides
D007004:Hypoglycemic Agents; D014044:Tolbutamide; C006913:carboxytolbutamide; C031014:hydroxymethyltolbutamide; D000096926:Benzenesulfonamides