ArticleDrug design, development and therapy2024
Determination of Nemonoxacin in Small Volumes of Rat Plasma and Bile by a Novel HPLC-Fluorescence Assay and Its Application to Disposition and Biliary Excretion Kinetics.
Article in Drug design, development and therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Nemonoxacin is a novel non-fluorinated quinolone antibiotic for the treatment of community-acquired pneumonia. To investigate the pharmacokinetics (PK) of nemonoxacin, a simple and sensitive high-performance liquid chromatography assay (HPLC) was needed. Methods: An HPLC method with fluorescence (FL) detection was developed for the quantification of nemonoxacin in plasma and bile. Ultraviolet (UV) and FL characteristics were examined for the optimal detection conditions. Nemonoxacin and the internal standard gatifloxacin were extracted from plasma utilizing ethyl acetate-isopropanol (70/30, v/v). For bile sample preparation, direct dilution with the mobile phase buffer was used. Chromatographic separation was achieved on a C6-phenyl column (5 μm, 25 cm × 4.6 mm i.d.) at 30 °C with a flow rate of 1 mL/min. The mobile phase was composed of methanol and 50 mM potassium dihydrogen phosphate containing 0.5% (v/v) triethylamine (pH 7.5) (45/55 and 35/65 (v/v) for plasma and bile samples, respectively). FL was measured at an emission wavelength of 465 nm with excitation at 285 nm. Results: The calibration curves were linear with a lower limit of quantification of 5 and 100 ng/mL in a small volume of plasma (50 μL) and bile (10 μL). The intra- and inter-day precision was within 9.0% and the accuracy was within 7.6% deviation of the nominal concentration. Nemonoxacin was stable under various storage/handling conditions tested. The method was successfully employed to describe the plasma and biliary profiles of nemonoxacin in rats following a single intravenous dose of 1 mg/kg. Nemonoxacin displayed two-compartment disposition kinetics. The bile-to-plasma area under concentration-time curve ratio (AUC Conclusion: A validated method was developed and found to be specific, precise and accurate. The applicability of this proposed method was substantiated in pharmacokinetic studies in rats.
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