Automated sub-ppm mass accuracy on an ESI-TOF for use with drug discovery compound libraries

Abstract

An automated, routine method to obtain sub-ppm accurate mass data on a benchtop electrospray ionization time-of-flight (ESI-TOF) mass spectrometer is described. Standards in the mass range 114 to 734 Da were analyzed over a 5-day period to demonstrate intra-and interday precision and mean mass accuracy less than 1 ppm. One hundred drug discovery pharmaceutical compounds were used to demonstrate an absolute average mass accuracy of 0.47 Ϯ 0.31 ppm. This is in contrast to previous reports of accurate mass analysis using time-of-flight mass spectrometry (TOFMS) technology that operates within 3 to 5 ppm. The same 100 samples were also analyzed using Fourier transform mass spectrometry (FTMS) technology and yielded comparable results to the TOFMS analysis. (J Am Soc Mass Spectrom 2007, 18, 1612-1616

Analytical strategies for LC–MS-based targeted metabolomics

“…However, time-of-flight (resolving power 10,000) [21,22] and Thermo Fisher Scientific's Orbitrap (resolving power 100,000) [25,26] offer the advantages of lower cost, greater ease of maintenance and use, and easier coupling to LC by ESI. In addition, Orbitrap offers excellent mass accuracy, in the range of 1-2 ppm.…”

“…In conjunction with liquid chromatography, ionization may be achieved using electrospray ionization (ESI), atmosphere pressure chemical ionization (APCI), or atmospheric pressure photoionization (APPI) [19]. Mass spectrometer options include quadrupoles and ion traps which offer good sensitivity but limited resolving power [20], or higher mass resolution instruments such as time-offlight (TOF) [21,22], Fourier transform ion cyclotron resonance (FTICR) [23,24] or Orbitrap [25,26]. The mass spectrometer can also be arranged in a tandem configuration, such as a triple quadrupole mass spectrometer.…”

Simultaneous Analysis of Conazole Fungicides in Garlic by Q-TOF Mass Spectrometer Coupled with a Modified QuEChERS Method

“…Q-TOF-MS is characterized with a highly reliable separation technic between multiple targets (Ferrerand Thurman, 2007;Gilbert-López et al, 2010), since it provides mass accuracies with an error in the range of 1 to 2 ppm (Wolff et al, 2001;Stroh et al, 2007).…”

Sub‐2 μm HPLC coupled with sub‐ppm mass accuracy for analysis of pharmaceutical compound libraries

“…It was not recognized until recently that TOF instrumentation could be made to operate routinely with mass accuracies at the sub-ppm level for pharmaceutical compounds [18]. Now that sub-ppm mass accuracy is routinely available using TOF technology, it is now possible to develop high-speed sub-ppm mass accurate LC/MS analyses that can be applied to every compound that enters a pharmaceutical company's library, which is the subject of this report.…”