In vivo metabolism of lidocaine in the rat. Isolation of urinary metabolites as pentafluorobenzoyl derivatives and their identification by combined gas chromatography-mass spectrometry.
The metabolism of a large dose (40 mg/kg intraperitoneally) of lidocaine (LIDO) in mature male Sprague-Dawley rats is described. Pentafluorobenzoyl chloride was used to derivatize the hydrolyzed urinary metabolites prior to extraction and analysis as pentafluorobenzoyl-derivatives by combined gas chromatography-mass spectrometry. Total ion and selected ion current (m/z 195; C6F5CO+) traces were recorded and metabolites of LIDO were readily identified. Only one major metabolite, 3-hydroxy-N-(N-ethylglycyl)-2,6-xylidine, was excreted in urine. A new metabolite, 3-hydroxy-N-glycyl-2,6-xylidine was also present in significant amounts, as well as minor quantities of four oxygenated metabolites of N-(N-ethylglycyl)-2,6-xylidine. Other known metabolites of LIDO, including 3-hydroxylidocaine, were excreted in trace quantities. The results suggest that metabolism of LIDO in rats may be age- and/or dose-dependent.
Coutts
R T
RT
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Torok-Both
G A
GA
Chu
L V
LV
Tam
Y K
YK
Pasutto
F M
FM
D000818:Animals; D001565:Benzoates; D001711:Biotransformation; D008401:Gas Chromatography-Mass Spectrometry; D007202:Indicators and Reagents; D008012:Lidocaine / Q000378:metabolism* / Q000652:urine; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D005464:Fluorobenzenes; D005466:Fluorocarbons
D001565:Benzoates; D007202:Indicators and Reagents; D008012:Lidocaine; C014737:pentafluorobenzoyl chloride; D005464:Fluorobenzenes; D005466:Fluorocarbons