title: Determination of a novel nonfluorinated quinolone, nemonoxacin, in human feces and its glucuronide conjugate in human urine and feces by high-performance liquid chromatography-triple quadrupole mass spectrometry.
abstract: Three methods were developed and validated for determination of nemonoxacin in human feces and its major metabolite, nemonoxacin acyl-β- d-glucuronide, in human urine and feces. Nemonoxacin was extracted by liquid-liquid extraction in feces homogenate samples and nemonoxacin acyl-β- d-glucuronide by a solid-phase extraction procedure for pretreatment of both urine and feces homogenate sample. Separation was performed on a C18 reversed-phase column under isocratic elution with the mobile phase consisting of acetonitrile and 0.1% formic acid. Both analytes were determined by liquid chromatography-tandem mass spectrometry with positive electrospray ionization in selected reaction monitoring mode and gatifloxacin as the internal standard. The lower limit of quantitation (LLOQ) of nemonoxacin in feces was 0.12 µg/g and the calibration curve was linear in the concentration range of 0.12-48.00 µg/g. The LLOQ of the metabolite was 0.0010 µg/mL and 0.03 µg/g in urine and feces matrices, while the linear range was 0.0010-0.2000 µg/mL and 0.03-3.00 µg/g, respectively. Validation included selectivity, accuracy, precision, linearity, recovery, matrix effect, carryover, dilution integrity and stability, indicating that the methods can quantify the corresponding analytes with excellent reliability. The validated methods were successfully applied to an absolute bioavailability clinical study of nemonoxacin malate capsule.
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Rd, Shanghai, 200040, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, 12 Wulumuqi Zhong Rd, Shanghai, 200040, China.
authors.forename: Gaoli
authors.initials: G
authors.lastname: He
authors.forename: Beining
authors.initials: B
authors.lastname: Guo
authors.forename: Jicheng
authors.initials: J
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wu
authors.forename: Guoying
authors.initials: G
authors.lastname: Cao
authors.forename: Yaoguo
authors.initials: Y
authors.lastname: Shi
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Tsai
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005243:Feces / Q000737:chemistry*; D020719:Glucuronides / Q000032:analysis* / Q000652:urine; D006801:Humans; D011804:Quinolines / Q000032:analysis* / Q000652:urine; D015363:Quinolones / Q000032:analysis* / Q000652:urine; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D020719:Glucuronides; D011804:Quinolines; D015363:Quinolones; C543520:nemonoxacin
keywords: LC-MS/MS; human urine and feces; metabolite; nemonoxacin; validation