Quantitative MS³ Using The AB SCIEX 6500 Hybrid Linear Ion Trap: Leveraging The Next Dimension Of Selectivity And Specificity

Since the acquisition of three AB SCIEX QTRAP® 6500 mass spectrometers at Charles River Laboratories in 2013, numerous assays have been developed which leverage the instruments’ improved sensitivity (up to 10-fold over the previous QTRAP 5500 platform) and increased dynamic range, the latter allowing quantitation between four and five orders of magnitude. The majority of developed assays have utilized the triple-stage quadrupole (QqQ) multiple-reaction monitoring (MRM) scan function, a process wherein a precursor ion is selected in the first resolving quadrupole (Q1), then axially accelerated and dissociated (i.e., fragmented) in the second RF-only quadrupole (q2), which contains pressurized nitrogen gas and functions as a collision cell. A first-generation progeny ion originating from the dissociative event in the collision cell is then transmitted through a third resolving quadrupole (Q3) to the detector. This “tandem” mass spectrometric sequence of events involving collisionally-activated dissociation (CAD) defines an MRM scan function, also referred to as MS/MS, with the first MS process being ion-formation, and the second, dissociation.