Assessment of Liquid Chromatography Tandem Mass Spectrometry Approaches for the Analysis of Ceftiofur Metabolites in Poultry Muscle

Abstract

Abstract The use of cephalosporin antibiotics in veterinary practice is likely to play an important role in the development of ß-lactam resistant bacteria. To detect off-label cephalosporin antibiotic usage an analytical method is needed that, besides the native compound, also detects active metabolites thereof. In this paper the applicability of three approaches for the quantitative analysis of ceftiofur using liquid chromatography coupled to tandem mass spectrometry is assesed, viz. (A) the analysis of ceftiofur, desfuroylceftiofur and/or desfuroylceftiofur cystein disulfide, (B) the derivatization of ceftiofur metabolites to desfuroylceftiofur acetamide and (C) the chemical hydrolysis using ammonia in order to produce a marker compound for ceftiofur. We found that approach A is not suited for quantitative analysis of total ceftiofur concentration nor for effectively detecting off-label use of ceftiofur. Approach B resulted in adequate quantitative results, but is considered to be a single compound method because it depends on the cleavage of a thioester group which is present in only a limited number of cephalosporin antibiotics. Approach C showed adequate quantitative results as well. In contrast to approach B, this approach is applicable to a range of cephalosporin antibiotics and therefore applicable as a broad quantitative screening of cephalosporin compounds in poultry tissue samples to indicate off-label use of cephalosporins in poultry breeding. Based on the research presented here, it is concluded that the multi-method following approach C is the most suited to detect off-label use of a range of cephalosporin antibiotics in the fight against emerging bacterial resistance.