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Stereospecific gas chromatographic/mass spectrometric assay of the chiral labetalol metabolite 3‐amino‐1‐phenylbutane
Author(s) -
Changchit A.,
Gal J.,
Zirrolli J. A.
Publication year - 1991
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.1200201202
Subject(s) - labetalol , chemistry , chromatography , enantiomer , selected ion monitoring , metabolite , gas chromatography , mass spectrometry , urine , gas chromatography–mass spectrometry , stereochemistry , biochemistry , medicine , blood pressure , radiology
We previously identified 3‐amino‐1‐phenylbutane (APB) as an oxidative N ‐dealkylated, metabolite of the antihypertensive agent labetalol. Labetalol has two asymmetric centers and is used clinically as a mixture of the four possible stereoisomers; APB has one asymmetric center. We now report an enantiospecific gas chromatographic/mass spectrometric assay for APB in urine. After adding the internal standard 1‐methyl‐2‐phenoxyethylamine and alkalinizing, the urine samples were extracted with ether. The extracts were derivatized with the optically active acid chloride prepared from ( S )‐α‐methoxy‐α‐trifluoromethylphenylacetic acid. The derivatives were separated by capillary gas chromatography and detected by electron capture negative ion chemical ionizatin mass spectrometry with selected ion monitoring. The derivative of the R enantiomer eluted first, and the [M – 32] − ions were monitored for both the drug and the internal standard. The method was linear in the 0.05–2.5 μ enantiomer −1 ml −1 range and had inter‐assay and intra‐assay coefficients of variation of <6%. The assay was used in the analysis of urine samples from a patient in labetalol therapy and no interference was found. Further studies are needed to elucidate the oxidative metabolism of labetalol and its stereochemical aspects.