HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAYS WITH FLUOROMETRIC DETECTION FOR MIVACURIUM ISOMERS AND THEIR METABOLITES IN HUMAN

Two high-performance liquid chromatographic assays coupled with fluorometric detection have been developed for the determination of mivacurium isomers (trans-trans, cis-trans and cis-cis) and their monoester and alcohol metabolites in human plasma. A novel solid-phase extraction procedure allowed good recovery of the mivacurium isomers (mean 98%) and their monoester metabolites (mean 83%), whereas the alcohol metabolites were analyzed after direct precipitation of plasma proteins. For all analytes, these assays proved to be sensitive (LOQ 3.9-15.6 ng/ml), reproducible (C.V.<15%) and accurate (>94%) over the therapeutic range of concentrations of mivacurium and its metabolites. These two methods were applied successfully to a pharmacokinetic study of mivacurium after a bolus dose of 0.15 mg/kg in anesthetized patients.