Enantioselective analysis of unbound tramadol, O-desmethyltramadol and N-desmethyltramadol in plasma by ultrafiltration and LC-MS/MS: Application to clinical pharmacokinetics

► Binding of drugs to plasma proteins can be stereoselective. ► Unbound concentrations of tramadol, M1 and M2 enantiomers were analyzed by MS/MS. ► Kinetics of tramadol and M2 was enantioselective in patients with neuropathic pain. ► Fraction unbound of tramadol enantiomers was higher than that of the (+)-M1.