AN IMPROVED METHOD FOR THE MEASUREMENT OF LIDOCAINE AND ITS METABOLITES IN RAT PLASMA

An improved method is described for the quantitation of lidocaine and its dominant metabolites in rat plasma, 3-hydroxy-lidocaine glucuronid e and 3-hydroxy-MEG-X glucuronide. Frozen plasma samples (100-200 mu l ) were thawed and deproteinated by precipitation with acetonitrile, be fore the conversion of glucuronidates into their respective hydroxylat ed forms by acid hydrolysis. After extraction with solid-phase C-18 ca rtridge chromatography, the metabolites phorus detection, without deri vativization. A detection limit of 0.005 mu g/ml for lidocaine and non glucuronidated metabolites and 0.01 mu g/ml for glucuronidated metabol ites was achieved. The method offers significant improvements in sensi tivity relative to existing techniques, which should be of specific be nefit to studies in which sample volume is limited, such as those conc erned with the pharmacokinetics of lidocaine metabolism in small-anima l pain state models.