A Simple LC/MS/MS Method for the Determination of Moxifloxacin N-Sulfate in Rat Plasma and Its Application in a Pharmacokinetic Study.
Moxifloxacin N-sulfate is one of the main metabolites of moxifloxacin in phase II metabolism mediated by sulfotransferases. In this study, a simple, rapid, and sensitive LC/MS/MS method with one-step protein precipitation with methanol was developed and validated to quantify the concentration of moxifloxacin N-sulfate in rat plasma. The chromatographic separation was accomplished by using an Agilent Extend C18 column (4.6×250 mm; 5 μm) with a mobile phase consisting of acetonitrile and distilled water (30:70, v/v) containing 5 mM ammonium formate (pH=8.82 adjusted by ammonia) at a flow rate of 1.0 mL/min. A triple quadrupole tandem mass spectrometer with electrospray ionization source was used as a detector operated by multiple reaction monitoring in the negative-ion mode with m/z 480.2/436.3. The calibration curve was linear ranging from 2 to 200 ng/mL. The intraday and interday precision values (RSD) were less than 7.10%, and the intraday and interday accuracy values (relative error) were within -0.40 to 4.99%. Stabilities of all QC samples were within general assay acceptability criteria according to the U.S. Food and Drug Administration guidelines. No considerable matrix effect was found. A pharmacokinetic study of moxifloxacin N-sulfate after a single oral dose of moxifloxacin in rats was carried out using this new method.
Peking University Health Science Center, School of Pharmaceutical Sciences, Department of Pharmaceutics, Beijing 100191, People's Republic of China.
Jian
J
Li
Yin
Y
Yuan
Rong
R
Fan
Qinghong
Q
Su
Siyuan
S
Wang
Tianyan
T
Zhou
Wei
W
Lu
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D024841:Fluoroquinolones / Q000493:pharmacokinetics*; D008297:Male; D000077266:Moxifloxacin; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077266:Moxifloxacin