N-Hydroxyamide metabolites of lidocaine. Synthesis, characterization, quantitation, and mutagenic potential.
Two possible N-hydroxyamide metabolites of lidocaine were synthesized and characterized. A combined technique utilizing chemical-ionization mass spectrometry and stable isotope labeling demonstrated that these potentially carcinogenic N-hydroxyamides were neither present in human urine after oral lidocaine administration nor during intravenous infusion of lidocaine for the treatment of ventricular arrhythmias. However, small amounts of 2,6-dimethylphenylhydroxylamine were detected in the urine of all subjects. Mutagenesis assays using the Ames test showed that neither the N-hydroxyamides nor the N-hydroxyarylamine produced revertant colonies above background levels using the Salmonella tester strain TA-1538.
D000818:Animals; D002273:Carcinogens / Q000138:chemical synthesis; D003903:Deuterium; D006801:Humans; D007553:Isotope Labeling; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000652:urine; D013058:Mass Spectrometry; D051379:Mice; D009153:Mutagens / Q000138:chemical synthesis*; D012475:Salmonella / Q000187:drug effects; D013237:Stereoisomerism
D002273:Carcinogens; D009153:Mutagens; D008012:Lidocaine; D003903:Deuterium