Sensitive liquid chromatography–tandem mass spectrometry method for the determination of cefixime in human plasma: Application to a pharmacokinetic study

Abstract

A sensitive and selective liquid chromatographic–tandem mass spectrometric (LC–MS–MS) method was developed to determine cefixime ((6 R,7 R)-7-[( Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino)acetamido]-8-oxo- 3-vinyl-5-thia-1-azabicyclo-[4,2,0]-oct-2-ene-2-carboxylic acid) in human plasma. After a simple protein precipitation using acetonitrile, the post-treatment samples were analyzed on a C 8 column interfaced with a triple quadrupole tandem mass spectrometer. Positive electrospray ionization was employed as the ionization source. The mobile phase consisted of acetonitrile–water–formic acid (40:60:0.5, v/v/v). The analyte and internal standard cefetamet were both detected by use of selected reaction monitoring mode. The method was linear in the concentration range of 0.05–8.0 μg/ml. The lower limit of quantification was 0.05 μg/ml. The intra- and inter-day relative standard deviation across three validation runs over the entire concentration range was less than 12.7%. The accuracy determined at three concentrations (0.05, 0.80 and 7.2 μg/ml for cefixime) was within ±2.0% in terms of relative error. Each plasma sample was chromatographed within 3.5 min. The method herein described was successfully applied for the evaluation of pharmacokinetic profiles of cefixime capsule in 24 healthy volunteers.