Validated HPLC Method for the Pharmacokinetic Study of Linezolid in Rats

Abstract

Linezolid is an oxazolidinone with potent antibacterial activity against multidrug resistant Gram-positive bacteria. This study aimed to develop and validate a sensitive, rapid and reliable high-performance liquid chromatography-photodiode array detector method for determining linezolid concentrations in the plasma and urine and to further characterize the pharmacokinetics of linezolid in rats. Chromatographic separation was performed using a SinoPak BEH C₁₈ column with isocratic elution (acetonitrile: water, 28:72, v/v). The retention times of linezolid and the internal standard are 3.30 and 5.20 min, respectively. The calibration curve for linezolid was linear over the concentration range of 0.25–50.0 μg/mL in rat plasma and 1.00–100.0 μg/mL in rat urine. Intra- and inter-assay precision values were below 9.00%, with accuracy ranging from 0.67% to 8.34%. Plasma samples were extracted using acetonitrile-mediated protein precipitation, and the recovery was > 93%. Following intragastric (63 mg/kg) and intravenous (25 mg/kg) administration of linezolid to rats, the area under the plasma concentration–time profile from time 0 to infinity were 224.5 and 86.4 μg·h/mL, total clearance were 0.29 and 0.30 L/h/kg, respectively. The cumulative urinary excretion rates of linezolid were 26.2%–27.5% for both administration routes. The presented method can certainly be used for routine analysis of linezolid in plasma and urine.