Clavulanic acid (CLV) is a betalactam (BL) which inhibits betalactamases activity and is frequently administered combined with amoxicillin (AX). Both BLs can be independently involved in allergic reactions. Indeed, selective immediate allergic reactions to CLV have recently been reported in 30% of patients allergic to the AX-CLV combination. Although protein haptenation with β-lactams is considered necessary to activate the immune system, currently there are no straight-forward detection tools for the study of protein haptenation by CLV. The aim of this study was to assess the suitability of two biotinylated analogues of CLV, CLV-B or CLV-TEG-B (containing the later a hydrophilic tetraethylenglycol linker), as probes to study protein haptenation by this β-lactam. Our results show that tagged CLV keeps some of the features of CLV, as the amide binding by which they haptenate proteins and it could constitute a valuable tool to identify protein targets for haptenation by CLV with high sensitivity to get insights into the activation of the immune system by CLV as well as mechanisms involved in allergy to β-lactams.