Broad spectrum drug screening using liquid chromatography quadrupole time of flight mass spectrometry: How valuable is retention time for identifying compounds?

Background: Broad spectrum drug screening, also known as systematic toxicological analysis or general unknown screening (GUS), is a method commonly used by clinical and forensic toxicology laboratories to detect a variety of drugs and metabolites in biological fluids. Recently, there has been much interest in liquid chromatography-high resolution mass spectrometry (LCHRMS) techniques for GUS as these instruments have excellent full-scan sensitivity and are therefore often operated in an untargeted manner. Untargeted data collection is especially attractive in the setting of GUS as it allows for the identification of unexpected compounds. Hybrid instruments, such as the quadrupole time-of-flight (QTOF) mass spectrometer, can collect full-scan TOF MS data followed by information dependent acquisition of product ion spectra. Compound identification is then based on comparing the precursor mass, isotope pattern, retention time and product ion spectrum to that of a reference standard.