Investigation of the pharmacokinetics and determination of tramadol in rabbit plasma by a high-performance liquid chromatograph-diode array detector method using liquid-liquid extraction

An HPLC system using a new, simple and rapid liquid-liquid extraction and high-performance liquid chromatography-diode array detector method (HPLC-DAD) detection was validated to determine tramadol concentration in rabbit plasma. The method described was applied to a pharmacokinetic study of intravenous tramadol injections in rabbits. The extraction with ethylacetate yielded good response. The recovery of tramadol from plasma averaged 90.40%. Serial plasma samples were obtained prior to, during and after completion of the infusion for determination of tramadol concentrations. Tramadol concentrations were measured using reverse-phase high-performance liquid chromatography and pharmacokinetic application with intravenous tramadol in rabbits revealed that tramadol followed one-compartment open model. Maximum plasma concentration (C a,) and area under the plasma concentration-time curve (AUC) for tramadol were 14.3 mug mL(-1) and 42.2 mug h mL(-1), respectively. The method developed was successfully applied to a simple, rapid, specific, sensitive and accurate HPLC method for investigation of the pharmacokinefics of tramadol in rabbit plasma. (C) 2004 Elsevier B.V. All rights reserved.