Determination of tramadol by capillary gas chromatography with flame ionization detection - Application to human and rabbit pharmacokinetic studies

A rapid, sensitive, precise and accurate capillary gas chromatographic assa y with flame ionization detection was developed for the determination of tr amadol in human, rabbit, pig and dog plasma. It is comprised of only a one- step extraction procedure with dichloromethane at pH 11.15 and gas chromato graphy on a capillary column. The recoveries of tramadol and meperidine (in ternal standard) were greater than 88%. Calibration graphs were linear over the concentration range 12.5-10 000 ng/ml with a coefficient of variation, both within-day and between-day, of less than 10% at any level. The limit of detection was 8 ng/ml of plasma based on signal-to-noise ratio of 3. Six other clinically used analgesics were investigated to check for potential interferences and their analytical conditions. The specificity of this assa y was checked with two major metabolites of tramadol (M-1: O-demethyltramad ol; M-2: N-demethyltramadol). Tramadol in plasma did not decompose signific antly at -20 degrees C for 56 days. Pharmacokinetic application with intrav enous tramadol in humans and rabbits revealed that tramadol followed a two- compartment open model with one distribution phase and one elimination phas e. The distribution and elimination half-lives in humans were 1.02 and 141. 9 min, The distribution and elimination half-lives in rabbits were 7.31 and 63.2 min, respectively. (C) 1999 Elsevier Science B.V. All rights reserved .