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5918008 
Journal Article 
Identification and quantitation of an oxidative metabolite of labetalol in sheep: pharmacokinetic and metabolic implications 
Yeleswaram, K; Rurak, DW; Kwan, E; Hall, C; Abbott, FS; Axelson, JE 
1992 
Yes 
Biological Mass Spectrometry
ISSN: 1052-9306 
21 
11 
534-540 
English 
1457468 
WOS:A1992JU83000002 
A sensitive and selective assay has been developed for the identification and quantitation of 3-amino-1-phenyl butane (3-APB), a metabolite of labetalol, in biological fluids using electron impact gas chromatography/mass-selective detection. Samples were extracted with n-hexane, derivatized with heptafluorobutyric anhydride and chromatographed on a cross-linked fused-silica capillary column. A positive EI spectrum was obtained using a mass-selective detector. Identification of the metabolite was accomplished using an authentic standard; quantitation was performed in the selected ion monitoring mode using ions m/z 345 (M+) and 132. The assay was linear over the calibration range of 0.5-1000 ng of the analyte and the intra-sample coefficients of variation were less than 12% in all cases. The absolute recovery of 3-APB following extraction from urine and bile was found to be 102.9 +/- 4.9% and 98.3 +/- 1.45% (mean +/- SEM) respectively. The minimum quantitation limit of the assay was 0.5 ng ml-1 (approximately 2 pg injected). Application of the assay in a pharmacokinetic-pharmacodynamic study of labetalol in sheep is demonstrated. The metabolite was detected in urine and bile samples obtained from adult non-pregnant sheep following labetalol administration. The cumulative amount of 3-APB excreted in urine over 24 h was found to be 71.55 micrograms in one animal following a 100 mg dose of labetalol. Evidence for biliary excretion, glucuronidation and sulfation of 3-APB was also found. 
Antihypertensive; Bioassay; Cross linked fused silica capillary column; Drug dosage; Drug therapy; Heptafluorobutyric anhydride; Labetalol; Mass selective detector; Oxidative metabolite; Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Gas chromatography; Body fluids; Metabolites; Derivatives; Pharmacokinetics; Metabolism; W4 462:BIOMEDICAL EQUIPMENT; W4 461.2:BIOLOGICAL MATERIALS; W 30965:Miscellaneous, Reviews; W4 801.2:BIOCHEMISTRY; W4 804.1:ORGANIC COMPOUNDS; W4 461.1:BIOMEDICAL ENGINEERING