Determination of zabofloxacin in rat plasma by liquid chromatography with mass spectrometry and its application to pharmacokinetic study.
The objective of the present study was to develop a rapid and sensitive method for the determination of zabofloxacin, a novel, broad-spectrum fluoroquinolone antibiotic, in rat plasma. Rat plasma samples were deproteinized with methanol, and then were injected into an LC-MS system for quantification. Zabofloxacin and enrofloxacin, which served as an internal standard, were analyzed by selected ion monitoring (SIM) at m/z transitions of 402 for zabofloxacin and 360 for the internal standard. The lower limit of quantification (LLOQ) was determined to be 10 ng/mL, with acceptable linearity ranging from 10 to 5000 ng/mL (R>0.999). The validation parameters for zabofloxacin, such as absolute matrix effect (107.7-116.0%), accuracy (92.5-101.1% for intra-day and 90.3-103.8% for inter-day), precision (7.7-10.2% for intra-day and 4.2-8.9% for inter-day), and stability in rat plasma (96.0-101.8%), were found to be acceptable according to the assay validation guidelines of the FDA (2001). Following oral administration of zabofloxacin to rats at a dose of 20mg/kg, the concentration of zabofloxacin in plasma was quantifiable in plasma samples collected up to 8h following zabofloxacin administration. The method described in the present study is applicable to routine pharmacokinetic studies in rats.
National Research Laboratory for Transporters Targeted Drug Design, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Hyo-Eon
HE
Jin
Kyeong-Ryoon
KR
Lee
In-Hyul
IH
Kang
Suk-Jae
SJ
Chung
Chang-Koo
CK
Shim
D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D024841:Fluoroquinolones / Q000097:blood* / Q000493:pharmacokinetics*; D006207:Half-Life; D008297:Male; D008832:Microchemistry / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C480202:zabofloxacin