Fragmentation of toxicologically relevant drugs in negative‐ion liquid chromatography–tandem mass spectrometry

Negative‐ion LC–MS analysis of drugs is applied far less frequently than positive‐ion LC–MS. Data on the interpretation of negative‐ion MS–MS spectra are even more scarce. Therefore, following the recent review on the class‐specific fragmentation of toxicologically relevant compounds in positive‐ion MS–MS, it was decided to perform a similar study in negative‐ion MS–MS. To this end, a set of over 500 negative‐ion MS–MS spectra was collected from three libraries applied in toxicological general unknown screening and systematic toxicological analysis. The compounds involved were classified by chemical and therapeutic class. The MS–MS spectra were manually interpreted and relevant interpretation data were searched for in the scientific literature. The emphasis in the discussion is on class‐specific fragmentation, because discussing fragmentation of all individual compounds would take far too much space. Negative‐ion MS–MS fragmentation is discussed for a wide variety of toxicologically relevant compounds, including dihydropyridine calcium channel blockers, diuretics, barbiturates, anti‐inflammatory drugs, anti‐diabetics, sulfonamide and betalactam antibiotics, and a number of classes of pesticides. © 2012 Wiley Periodicals, Inc. Mass Spec Rev 31:626–665, 2012