title: 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.
abstract: 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.
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Rd, Shanghai, 200040, China.
authors.forename: Beining
authors.initials: B
authors.lastname: Guo
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jicheng
authors.initials: J
authors.lastname: Yu
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wu
authors.forename: Yaoguo
authors.initials: Y
authors.lastname: Shi
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Tsai
mesh_terms: D000293:Adolescent; D000328:Adult; D002681:China; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004355:Drug Stability; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D015363:Quinolones; C543520:nemonoxacin