Determination of cefuroxime lysine in rat brain microdialysates by ultra‐fast liquid chromatography with UV and tandem mass spectrometry: application to an acute toxicokinetic study

Abstract

Cefuroxime lysine is a new second-generation cephalosporins, which can penetrate the blood-brain barrier to cure the meningitis. In order to investigate its acute toxicokinetic study after intraperitoneal injection of 675 mg/kg cefuroxime lysine, a sensitive and clean ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method for the determination of cefuroxime lysine in microdialysate samples was developed and validated, which was compared with UFLC-UV as a reference method. Chromatographic separation was performed on a Shim-pack XR-ODS C18 column (75 × 3.0 mm, 2.2 µm), with an isocratic elution of 0.1% formic acid in acetonitrile-0.1% formic acid in water (45:55, v/v) for LC-MS and acetonitrile-20 mm potassium dihydrogen phosphate (pH 3.0,20:80, v/v) for LC-UV. The lower limit of detection was 0.01 µg/mL for LC-MS and 0.1 µg/mL for LC-UV method, with the same corresponding linearity range of 0.1-50 µg/mL. The intra- and inter-day precisions (relative standard deviation) for both methods were from 1.1 to 8.9%, while the accuracy was all within ±10.9%. The results of both methods were finally compared using paired t-test; the results indicated that the concentrations measured by the two methods correlated significantly (p < 0.05), which suggested that the two methods based on LC-MS and LC-UV were suitable for the acute toxicokinetic study.