Ultrahigh pressure liquid chromatography–(tandem) mass spectrometry in human sports drug testing: Possibilities and limitations

Doping control analytical laboratories for human sports predominantly employ nowadays chromatographic–mass spectrometric test methods for routine, high throughput screening and confirmation assays concerning low and high molecular mass analytes. Liquid chromatography–(tandem) mass spectrometry [(LC–MS(/MS)] and particularly ultrahigh pressure liquid chromatography (UHPLC)–MS/MS instruments have become devices of choice due to their indispensable capabilities that compensate for limitations inherent to other commonly used strategies such as immunological and gas chromatography–(tandem) mass spectrometry [(GC–MS(/MS)]-based detection methods. UHPLC–MS/MS-based assays at low mass spectrometric resolution have been established allowing for fast and sensitive targeted analyses focusing on pre-selected target analytes with diagnostic precursor–product ion pairs. Combining UHPLC to high resolution/high accuracy MS(/MS) further expanded the targeted approach (i.e., plotting extracted ion chromatograms of protonated or deprotonated molecules as well as product ions measured with accurate masses) toward non-targeted analyses enabling also retrospective data mining. In this review, recent applications of UHPLC–MS/MS in sports drug testing procedures published between 2008 and 2012 are presented and advantages as well as limitations in a short- and long-term perspective are discussed.