A gas chromatographic assay for tocainide carbamoyl-O-beta-D-glucuronide:quantitation of the base hydrolyzed product, 3-(2',6'-xylyl)-5-methylhydantoin.
Quantitation of tocainide carbamoyl-O-B-D-glucuronide, a major metabolite of the antiarrhythmic agent, tocainide, was previously reported using sodium hydroxide hydrolysis (pH greater than 12) of the glucuronide followed by gas chromatographic analysis of the hydrolyzed product, 3-(2',6'-xylyl)-5-methylhydantoin. In this investigation, the hydantoin was found to undergo rapid degradation during base hydrolysis of the tocainide glucuronide. The hydantoin was synthesized and its hydrolysis in sodium hydroxide (pH greater than 12) was found to follow first-order kinetics with an estimated half-life of 24.6 minutes. This spontaneous and rapid degradation of the hydantoin during hydrolysis of the tocainide glucuronide may result in underestimation of the hydantoin. To correct for the degradation of the hydantoin, a gas chromatographic assay with a timed, base-hydrolysis calibration protocol was designed. To demonstrate the applicability of this assay, the elimination kinetics of tocainide and the tocainide carbamoyl glucuronide were studied in three healthy male volunteers after a single 200 mg oral dose of tocainide hydrochloride. From urine data, the elimination half-life of tocainide was approximately 15.5 hours. The urinary excretion half-life of the tocainide carbamoyl glucuronide was approximately 13.8 hours.
Kwok
D W
DW
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
McErlane
K M
KM
Axelson
J E
JE
D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics; D002138:Calibration; D002849:Chromatography, Gas; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D006827:Hydantoins / Q000032:analysis*; D006868:Hydrolysis; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D008297:Male; D015203:Reproducibility of Results; D012972:Sodium Hydroxide; D016677:Tocainide / Q000031:analogs & derivatives
D000889:Anti-Arrhythmia Agents; D006827:Hydantoins; D016677:Tocainide; D012972:Sodium Hydroxide; C031395:3-(2,6-xylyl)-5-methylhydantoin; C033805:tocainide carbamoyl O-beta-glucuronide; D008012:Lidocaine