Exact Matrix-matching Calibration by Standard Addition-Isotope Dilution-Liquid Chromatography/Mass Spectrometry for the Accurate Determination of Chloramphenicol in Infant Formula

We consistently observed a bias in the results for determination of chloramphenicol (CAP) in infant formula by isotope dilution-liquid chromatography/mass spectrometry (ID-LC/MS). Various matrix interferences from infant formula eventually can result in bias during the ID-LC/MS analysis. We tried to optimize LC conditions to minimize matrix effects by separating significant matrix interferences from the analyte and the internal standard, but some level of bias remained. To eliminate the bias due to the matrix effects, we used a standard addition-isotope dilution-liquid chromatography/mass spectrometry (SA-ID-LC/MS) method for CAP analysis. In the SA-ID-LC/MS method, standard addition techniques were combined with IDMS for exact matrix matching while keeping the isotope dilution techniques as a tool for accurate correction of recovery in sample preparation processes. The method provided accurate analytical results for target analyte in the range of 1 µg/kg with a relative expanded uncertainty of 3%.