Multiple reaction monitoring (MRM)-profiling with biomarker identification by LC-QTOF to characterize coronary artery disease

Metabolite profiling by mass spectrometry (MS) is an area of interest for disease diagnostics, biomarker discovery, and therapeutic evaluation. A recently developed approach, multiple reaction monitoring (MRM)-profiling, searches for metabolites with precursor (Prec) and neutral loss (NL) scans in a representative sample and creates a list of ion transitions. These are then used in an MRM method for fast screening of individual samples and discrimination between healthy and diseased. A large variety of functional groups are considered and all signals discovered are recorded in the individual samples, making this a largely unsupervised method. MRM-profiling is described here and then demonstrated with data for over 900 human plasma coronary artery disease (CAD) samples. Representative pooled samples for each condition were interrogated using a library of over a hundred Prec and NL scans on a triple quadrupole MS. The data from the Prec and NL experiments were converted into ion transitions, initially some 1266 transitions. Each ion transition was examined in the individual samples on a time scale of milliseconds per transition, which allows for rapid screening of large sample sets (