Premium
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
Author(s) -
Guo Beining,
Zhang Jing,
Yu Jicheng,
Wu Xiaojie,
Shi Yaoguo,
Tsai ChengYuan
Publication year - 2012
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.2699
Subject(s) - chemistry , chromatography , protein precipitation , pharmacokinetics , liquid chromatography–mass spectrometry , tandem mass spectrometry , selected reaction monitoring , mass spectrometry , antibacterial agent , gatifloxacin , electrospray ionization , sample preparation , high performance liquid chromatography , levofloxacin , antibiotics , pharmacology , biochemistry , medicine
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. Copyright © 2012 John Wiley & Sons, Ltd.