Liquid chromatography coupled to tandem mass spectrometry and high resolution mass spectrometry as analytical tools to characterize multi-class cytostatic compounds

Cytostatic compounds used in the treatment of cancer have emerged as a new generation of water contaminants due to the continuous amounts administered to patients and to the fact that a variable proportion is excreted unchanged. In this study, we have evaluated the performance of liquid-chromatography–tandem mass spectrometry (LC–MS/MS) and high resolution mass spectrometry using an Orbitrap analyzer (LC–HRMS) for the multiresidue determination of multi-class cytostatic compounds. In a first step, ionization conditions were tested in positive electrospray mode and optimum fragmentation patterns were determined. For LC–MS/MS, two selected reaction monitoring (SRM) transitions were optimized and for LC–HRMS, the molecular ion with 5 ppm error and two product ions were defined. Following, the chromatographic conditions were optimized considering that compounds analyzed have a very different chemical structure and chromatographic behavior. The best performance was obtained with a Luna C18 column, which permitted the separation of the 26 compounds in 15 min. Finally, the performance of LC–MS/MS and LC–HRMS was compared in terms of linearity, sensitivity, intra and inter-day precision and overall robustness. While LC–MS/MS provided good identification capabilities due to selective SRM transitions, LC-Orbitrap proved to be 100 times more sensitive. This study provides a comprehensive overview on the MS conditions to determine the outmost used cytostatic compounds and provides a spectral library to be used for the identification of these compounds in water or biological matrices.

► Cytostatic compounds were fully characterized by LC–MS/MS and LC-Orbitrap-MS.
► Good chromatographic resolution was obtained at Rs = 50,000 FWHM.
► Limits of detection ranged from 0.005 to 0.15 ng, being Orbitrap more sensitive.
► The multiresidual analytical method can be applied in monitoring studies.