Tandem-in-Time Mass Spectrometry as a Quantitative Bioanalytical Tool

Abstract

Tandem-in-time mass spectrometry, as implemented on an ion-trap detector (ITD), is the process whereby precursor ions are created, stored in a radio frequency (rf) trapping field, and then sequentially fragmented to form product ions by application of additional rf waveforms. As with any form of tandem mass spectrometry (MS/MS), tandem-in-time MS is highly selective, by virtue of both mass discrimination and specific gas-phase chemistry. Beyond this, however, tandem-in-time MS offers ion throughput efficiency and cost advantages over either quadrupole or sector instruments. This paper will describe the use of capillary gas chromatography combined with tandem-in-time mass spectrometry to quantify a novel therapeutic agent extracted from human plasma. For an example compound, a quantitation limit of 25 pg/mL (S/N approximately 10, 15 fmol on-column) was attained out of plasma. The interday imprecision was < or = 12.2% over a dynamic range extending to 10 ng/mL. Due to favorable ionization conditions for the test analytes, electron ionization resulted in formation of M+ ions, with very little fragmentation, allowing for maximum assay sensitivity. Although method characterization and validation demonstrated adequate instrumental performance, some lack of ruggedness was encountered during routine application.