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Identification and quantitation of an oxidative metabolite of labetalol in sheep: Pharmacokinetic and metabolic implications
Author(s) -
Yeleswaram Krishnaswamy,
Rurak Dan W.,
Kwan Eddie,
Hall Caroline,
Abbott Frank S.,
Axelson James E.
Publication year - 1992
Publication title -
biological mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1052-9306
DOI - 10.1002/bms.1200211103
Subject(s) - metabolite , chromatography , labetalol , chemistry , urine , pharmacokinetics , glucuronidation , detection limit , analyte , selected ion monitoring , pharmacology , gas chromatography–mass spectrometry , mass spectrometry , biochemistry , microsome , biology , medicine , in vitro , blood pressure
A sensitive and selective assay has been developed for the identification and quantitation of 3‐amino‐1‐phenylbutane (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 chromato‐graphed 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 extracton 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 (≈ 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 μg in one animal following a 100 mg dose of labetalol. Evidence for biliary excretion, glucuronidation and sulfation of 3‐APB was also found.