title: 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.
authors.affiliation: Department of Pharmacokinetics and Drug Metabolism, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48189, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Rossi
authors.forename: K L
authors.initials: KL
authors.lastname: Hoffman
authors.forename: N
authors.initials: N
authors.lastname: Janiczek-Dolphin
authors.forename: H
authors.initials: H
authors.lastname: Bockbrader
authors.forename: T D
authors.initials: TD
authors.lastname: Parker
mesh_terms: D002800:Cholinesterase Inhibitors / Q000097:blood; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*
chemical_list: D002800:Cholinesterase Inhibitors