Determination of tramadol by capillary gas chromatography with flame ionization detection. Application to human and...

A rapid, sensitive, precise and accurate capillary gas chromatographic assay with flame ionization detection was developed for the determination of tramadol 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 chromatography on a capillary column. The recoveries of tramadol and meperidine (internal 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 assay was checked with two major metabolites of tramadol (M1: O-demethyltramadol; M2: N-demethyltramadol). Tramadol in plasma did not decompose significantly at -20 degrees C for 56 days. Pharmacokinetic application with intravenous tramadol in humans and rabbits revealed that tramadol followed a two-compartment open model with one distribution phase and one elimination phase. 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.