Characterization of drug-related impurities using UPLC-QTrap-MS/MS in three scan modes: Application to daptomycin

Abstract

A new non-targeted screening strategy was developed for the detection and relative quantification of known and potentially unknown drug-related impurities in the active pharmaceutical ingredient daptomycin using ultra-high performance liquid chromatography, coupled with hybrid triple quadrupole-linear ion trap electrospray ionization mass spectrometry in three different modes. The precursor ion scan mode was first applied using the m/z transitions of 159.2, 313.2, and 341.2 for rapid screening of all daptomycin-related impurities. Precursor ions detected at specific retention times were selected, fragmented, and focused in enhanced product ion scan mode to obtain secondary ion mass spectra and identify drug-related impurities. Finally, each potential compound was relatively quantified in multiple reaction monitoring mode. Repeatability experiments suggest that this impurity profiling method is a reliable strategy for identifying unknown impurities in daptomycin and other drugs.