RESUMO
A rapid and reliable analytical method is described for the simultaneous determination of RWJ-38705 (tramadol N-oxide) and several of its major metabolites in the plasma of Sprague-Dawley rats and Beagle dogs. Sample preparation using solid phase extraction was followed by reversed phase liquid chromatography (LC) coupled with tandem mass spectrometric (MS/MS) detection in the positive ionization mode. The assay was linear for all analytes over concentrations ranging from approximately 6 to 2000 ng/ml. The inter-assay reproducibility was generally less than 15% while accuracy values were within 13% of theoretical. The overall recovery of the analytes ranged from approximately 40 to 64% in rat plasma and 53-75% in dog plasma. This assay has proven to be sensitive, specific and reproducible, and it has been readily implemented in preclinical PK studies. Representative plasma concentration versus time profiles resulting from administration of TNO to rats and dogs are presented in this communication.
Assuntos
Anticonvulsivantes/metabolismo , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Tramadol/análogos & derivados , Administração Oral , Animais , Anticonvulsivantes/sangue , Anticonvulsivantes/farmacocinética , Cromatografia Líquida de Alta Pressão , Cães , Injeções Intravenosas , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Tramadol/sangue , Tramadol/metabolismo , Tramadol/farmacocinéticaRESUMO
A rapid high-performance liquid chromatographic (HPLC) method for the determination of levofloxacin in human plasma and urine has been validated. A single-step liquid-liquid extraction procedure was used to isolate levofloxacin from the biological matrix prior to quantitative analysis. The compound was separated on an Inertsil C18 reversed-phase HPLC column and quantified by measuring the UV absorbance at 330 nm. The stereospecificity was achieved in the ligand-exchange mode by incorporating chiral reagents directly into the HPLC mobile phase. Ciprofloxacin was used as the internal standard. The method was linear from 0.08 to 5.18 micrograms ml-1 of levofloxacin in plasma and from 23 to 1464 micrograms ml-1 in urine. The overall utility of the method is reflected in its high sample throughput and easy adaptability to robotic automation, thus making the procedure suitable for pharmacological and pharmacokinetic studies of levofloxacin.
