Fluorescence Detection of Zabofloxacin, a Novel Fluoroquinolone Antibiotic, in Plasma, Bile, and Urine by HPLC: The First Oral and Intravenous Applications in a Pharmacokinetic Study in Rats

Hyo Eon Jin, In Hyul Kang, Chang Koo Shim
2011 Journal of Pharmacy & Pharmaceutical Sciences  
Purpose: To develop an HPLC method using fluorescence detection for the pharmacokinetic evaluation of levels of zabofloxacin, a novel broad spectrum fluoroquinolone antibiotic, in the plasma, bile and urine of rats. Methods: A simple reversed-phase HPLC method using a C18 column with fluorescence detection was developed and validated for the simultaneous determination of zabofloxain and enrofloxacin as an internal standard. The plasma sample was treated with methanol for protein precipitation,
more » ... ein precipitation, and treatment of the bile and urine samples included deproteinization and extraction using chloroform. The applicability of the developed assay method to pharmacokinetic studies of zabofloxacin in rats was examined. Zabofloxacin was intravenously and orally administered to rats at a dose of 20 mg/kg. Results: The limits of quantification (LOQ) was determined to be 50 ng/mL for the plasma with acceptable linearity ranging from 50 to 25,000 ng/mL (R>0.999), and 0.5 μg/mL for the bile and urine samples with acceptable linearity ranging from 0.5 to 100 μg/mL (R>0.999). The validation parameters for zabofloxacin were found to be acceptable according to FDA assay validation (2001). While zabofloxacin in plasma and urine has been stable in all tested handling conditions, it has been unstable in bile during freeze-thaw cycles for 24 h at room temperature. Following intravenous and oral administration of zabofloxacin to rats at a dose of 20 mg/kg, concentration was quantifiable in plasma for up to 8 h. The bioavailability of zabofloxacin was 27.7%, and it was excreted into bile and urine at about 8% each per oral administration. Conclusions: These observations suggest that a validated assay can be used in pharmacokinetic studies of zabofloxacin in small animals. Due to the limited stability of zabofloxcin in rat bile, freeze-thaw cycles or prolonged handling at room temperature is not recommended. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
doi:10.18433/j3j592 fatcat:ucgdltydbjhvjju4bhedzn3xvi