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.

Acetylation and pentafluorobenzoylation of lidocaine metabolites in aqueous solution and identification of derivatives by combined gas chromatography/mass spectrometry.

Known and possible phenolic and primary and secondary amine metabolites of lidocaine were added to urine from drug-naive rats. These metabolites were derivatized in this aqueous medium by acetylation with acetic anhydride or by pentafluorobenzoylation with pentafluorobenzoyl chloride. The derivatives were simultaneously extracted into an organic solvent. The products were separated by gas chromatography (flame ionization detection for acetates and electron-capture detection for pentafluorobenzoates) and identified by combined gas chromatography/mass spectrometry. Mass spectral fragmentation pathways were readily deduced; diagnostic fragment ions were identified and were valuable for characterization purposes. Structural isomers could be distinguished on the basis of their GC retention times. Extractive derivatization using pentafluorobenzoyl chloride is an attractive analytical procedure for the identification of phenolic and dealkylated metabolites of lidocaine.

Gas chromatographic separation of optically active anti-inflammatory 2-arylpropionic acids using (+)- or (-)-amphetamine as derivatizing reagent.

A method is described for the derivatization of several non-steroidal anti-inflammatory arylalkanoic acids (ibuprofen, ketoprofen, naproxen, fenoprofen, flurbiprofen, pirprofen, cicloprofen, tiaprofenic acid, etodolic acid) with optically active amphetamine. The usefulness of this reagent compared to alpha-methylbenzylamine is described. The enantiomers are separated as diastereoisomers using capillary gas chromatography with nitrogen-phosphorus detection. The procedure is readily applied to the quantification of the enantiomers in urine and plasma samples.

Gas-liquid chromatographic determination of aniline metabolites of substituted urea and carbamate herbicides in aqueous solution.

A simple gas-liquid chromatographic (GLC) method has been developed which provides sensitivity and specificity for the analysis of complex mixtures of the commonly occurring herbicide metabolites aniline, 3-chloroaniline, 4-chloroaniline, 4-bromoaniline, and 3-chloro-4-methylaniline. All of these anilines react with acetic anhydride directly in basified aqueous solution. Further reaction of the acetylated anilines with trifluoroacetic anhydride gave diacyl derivatives which were readily resolved by gas chromatography. The structures of the N-acetylated and N-trifluoroacetylated derivatives of benzylamine (internal standard) and the anilines were confirmed by GLC-mass spectrometry. In distilled water the minimum detectable concentrations of aniline and the substituted anilines, using electron capture GLC, are 0.1 nmole/100 mL and 0.05 nmole/100 mL, respectively. The detection limit for the anilines is 1 nmole/100 mL distilled water, using GLC with flame ionization detection. The technique was applied to the determination of anilines added to urine samples obtained from the general population.

Application of a direct aqueous acetylation technique to the gas chromatographic quantitation of nitrophenols and 1-naphthol in environmental water samples.

An improved method for the determination of low levels of nitrophenols in aqueous samples has been developed. The method is based on the gas chromatographic analysis of phenols as acetate derivatives which have been prepared directly in water. Recoveries of 97% or greater were obtained from aqueous solutions containing nitrophenols in concentrations ranging from 25 to 100 microgram/l. Concentrations as low as 1 microgram/l were easily detected. Nitrophenols appear to exhibit some resistance to degradation by microorganisms indigenous to the Athabasca River. Water samples to which 139 microgram/l each of o- and p-nitrophenol were added did not show evidence of microbial metabolism over a two week interval. Under identical conditions 100 microgram/l of m-cresol was metabolized within a 3-day period.