Electrospray ionization collision-induced dissociation tandem mass spectrometry of amoxicillin and ampicillin and their degradation products

Abstract

RATIONALE: Detailed analysis of the literature results on the electrospray ionization mass spectrometry (ESI-MS) fragmentation of amoxicillin and ampicillin, and their comparison with our results, have revealed some incorrect suggestions or incomplete interpretations of mass spectra of these compounds. Therefore, this paper contains a comprehensive discussion devoted to the ESI-MS/MS of ampicillin and amoxicillin as well as their degradation products, namely products of hydrolysis and methanolysis. METHODS: Electrospray ionization collision-induced dissociation tandem mass (ESI-CID-MS/MS) spectra and accurate mass measurements were made on a quadrupole time-of-flight (Q-tof) mass spectrometer. Hydrolysis of the antibiotics was performed by heating, for a few hours, their aqueous solutions adjusted to pH 10. Methanolysis of the antibiotics was performed by heating their methanol solutions for a few minutes. Additionally, mass spectra of isotope-labeled compounds were also obtained. RESULTS: A number of fragment ions, previously wrongly interpreted or not interpreted, have been rationalized. For example, formation of an abundant fragment at m/z 208 originating from the protonated amoxicillin molecule (ion [Amox + H]+) was previously rationalized as a result of breaking of two bonds of the β-lactam ring. We found that this fragment ion had to be formed by the loss of ammonia and breaking of three bonds of the bicyclic system. CONCLUSIONS: The discussion presented enables a better understanding of the MS decompositions of amoxicillin and ampicillin as well as their degradation products. MS decomposition is used for the determinations of these compounds, when the so-called multiple-reaction monitoring is applied during liquid chromatography (LC)/ESI-MS analysis. Thus, better understanding of MS decompositions of the above compounds seems to be important. Copyright © 2014 John Wiley & Sons, Ltd.