72998-95-9Relevant academic research and scientific papers
Preparative high-performance liquid chromatography and preparative thin-layer chromatography isolation of tocainide carbamoyl-O-β-D-glucuronide: Structural characterization by gas chromatography-mass spectrometry and fast atom bombardment-mass spectrometry
Kwok,Pillai,Vaughan,Axelson,McErlane
, p. 857 - 861 (1990)
Tocainide carbamoyl-O-β-D-glucuronide, a major urinary metabolite of the antiarrhythmic drug tocainide [2-amino-N-(2',6'-xylyl)propanoxylidide], was isolated by preparative-TLC and preparative-HPLC. The isolated glucuronide was hydrolyzed in sodium hydroxide (pH > 12) to 3-(2',6'-xylyl)-5-methylhydantoin. This hydantoin product was also identified when tocainide was reacted with urea in urine. Structural characterization of the isolated tocainide glucuronide was carried out using GC-MS of the permethylated derivative. The molecular ion of the permethylated glucuronide was not observed, but ion fragments at m/z 232(244), 277(288), and 334(349) were found to correspond to the postulated novel carbamoyl ester structure of the permethylated (perdeuteromethylated) glucuronide. Structural evidence for the underivatized tocainide glucuronide was obtained using fast atom bombardment-MS. The [M+H]+ ion at m/z 413 was observed. Characteristic sodium ion adducts [M+Na]+ and [M-H+2Na]+ were also observed at m/z 435 and 457, respectively.
Tocainide conjugation in humans: novel biotransformation pathway for a primary amine
Elvin,Keenaghan,Byrnes,Tenthorey,McMaster,Takman,Lalka,Manion,Baer,Wolshin,Meyer,Ronfeld
, p. 47 - 49 (2007/10/02)
The metabolism of tocainide, an experimental antiarrhythmic drug, was studied in humans. Urinary excretion of unchanged drug was 28-55% in 24 hr after oral dosing. Urine hydrolysis with hydrochloric acid or β-glucuronidase increased tocainide recovery to 55-79%. Saccharo-1,4-lactone inhibited the β-glucuronidase-mediated tocainide recovery increase. Adjustment of urine to pH 13 produced a compound identified as 3-(2,6-xylyl)-5-methylhydantoin. Evidence suggests that it was derived from the same metabolite that formed the additional tocainide after acid or β-glucuronidase treatment. Tocainide carbamoyl O-β-D-glucuronide is the structure proposed for the metabolite. The suggested pathway for its formation involves the addition of carbon dioxide to the amino nitrogen of tocainide followed by uridine diphosphate-glucuronic acid conjugation.
