A liquid chromatography-tandem mass spectrometry assay for the determination of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, in human plasma and urine and its application to a single-dose pharmacokinetic study in healthy Chinese volunteers.

Nemonoxacin (TG-873870) is a novel C-8-methoxy nonfluorinated quinolone with higher activity than ciprofloxacin, levofloxacin and moxifloxacin against Gram-positive pathogens including methicillin-susceptible or methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae with various resistant phenotypes. A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated to determine the concentration of nemonoxacin in human plasma and urine. Protein precipitation and liquid-liquid extraction were employed for plasma and urine sample preparations, respectively, and extract was then injected into the system. Separation was performed on a C(18) reversed-phase column using acetonitrile-0.1% formic acid as a mobile phase. Both analyte and internal standard (gatifloxacin) were determined using electrospray ionization and the MS data acquisition via the selected reaction monitoring in positive-ion mode. The lower limit of quantification was 5 ng/mL and the calibration curves were linear in the concentration range of 5-1000 ng/mL. The accuracy, precision, selectivity, linearity, recovery, matrix effect and stability were validated for TG-873870 in human plasma and urine. The method was successfully applied to a pharmacokinetic study enrolling 12 healthy Chinese volunteers administered nemonoxacin malate capsules.

RCT Entities:   Population Interventions Outcomes