Fragmentation of toxicologically relevant drugs in positive-ion liquid chromatography–tandem mass spectrometry



The identification of drugs and related compounds by LC–MS–MS is an important analytical challenge in several application areas, including clinical and forensic toxicology, doping control analysis, and environmental analysis. Although target-compound based analytical strategies are most frequently applied, at some point the information content of the MS–MS spectra becomes relevant. In this article, the positive-ion MS–MS spectra of a wide variety of drugs and related substances are discussed. Starting point was an MS–MS mass spectral library of toxicologically relevant compounds, available on the internet. The positive-ion MS–MS spectra of ∼570 compounds were interpreted by chemical and therapeutic class, thus involving a wide variety of drug compound classes, such benzodiazepines, beta-blockers, angiotensin-converting enzyme inhibitors, phenothiazines, dihydropyridine calcium channel blockers, diuretics, local anesthetics, vasodilators, as well as various subclasses of anti-diabetic, antidepressant, analgesic, and antihistaminic drugs. In addition, the scientific literature was searched for available MS–MS data of these compound classes and the interpretation thereof. The results of this elaborate study are presented in this article. For each individual compound class, the emphasis is on class-specific fragmentation, as discussing fragmentation of all individual compounds would take far too much space. The recognition of class-specific fragmentation may be quite informative in determining the compound class of a specific unknown, which may further help in the identification. In addition, knowledge on (class-specific) fragmentation may further help in the optimization of the selectivity in targeted analytical approaches of compounds of one particular class. © 2011 Wiley Periodicals, Inc., Mass Spec Rev 30:626–663, 2011