Accessing Higher Order Mathieu Space Stability Zones to Narrow Isolation Widths Using Digital Quadrupole Time-of-Flight Mass Spectrometry

Digital quadrupoles are driven with rectangular RF waveforms and, through duty cycle control, can access higher-order Mathieu space stability zones (HZs) using comparatively low voltages. Analytically, accessing these zones remains attractive as HZs exhibit higher resolving powers ((<i>m</i>/<i>z</i>)/(Δ<i>m</i>/<i>z</i>)) compared to the conventional quadrupole operation in zone (1,1). Presented here is a modification of a commercial quadrupole time-of-flight (Q-TOF) equipped with a low-voltage digital waveform driver to navigate the filtering quadrupole in the HZs. We demonstrate that a digital quadrupole operating in zones (3,1) and (3,2) achieves a narrowed isolation window for analytes up to 690 and 1543 <i>m</i>/<i>z</i>, respectively, compared to conventional operational modes. Experimental trends suggest this performance to continue to approximately 900 <i>m</i>/<i>z</i> in zone (3,1) and 2500 <i>m</i>/<i>z</i> in zone (3,2). These narrowed isolation windows were utilized to generate MS/MS data from a mixture of <i>m</i>-hydroxybenzoylecgonine (306 <i>m</i>/<i>z</i>) and cocaine-d3 (307 <i>m</i>/<i>z</i>), which exhibited minimal chimeric nature without the use of deconvolution software. The development of hybrid systems capable of both sine and digital operation provides a mechanism to maximize selectivity of the HZs while maintaining the benefits of traditional modes of operation. Minimizing chimeric interferences is of particular importance, and the narrow isolation widths afforded by HZs are readily accessible using tandem instruments for analytes <2500 <i>m</i>/<i>z</i>.