Suitability of tetrahydofuran as a dopant and the comparison to other existing dopants in dopant-assisted atmospheric pressure photoionization mass spectrometry in support of drug discovery.
In this paper, we investigated the suitability of tetrahydofuran (THF) as a dopant and compared it against other common dopants for atmospheric pressure photoionization mass spectrometry (APPI-MS). In a systematic analysis of 37 drug standards and 100 Wyeth proprietary drug candidates, THF was found to increase ionization efficiency as high as 33-fold when introduced through a syringe pump at a flow rate of 20 microL/min, and as high as 114-fold when introduced through the mobile phase at 100 microL/min. As a dopant, THF is as effective as acetone, better than anisole, and slightly less effective than toluene for the majority of the test compounds. The increase in ionization efficiency by THF was found to be compound-dependent. THF was more effective in facilitating the ionization of polar compounds than of non-polar compounds. With THF, toluene and acetone as dopants, a single type of molecular ion ([M+H](+) or M(+*)) is produced for analyte molecules. However, anisole can cause the formation of an ion cluster for polar analytes. The cluster contains [M-2H+H](+), M(+*), and [M+H](+) ions with varied ratios. This complexity may make interpretation of spectra difficult for unknown compounds when complimentary data are not available. Our findings indicate that THF is a suitable dopant in the daily usage for increasing ionization efficiency, especially when THF is used as the mobile phase or as an organic modifier in the mobile phase.
Cai
Yanxuan
Y
Discovery Analytical Chemistry, Chemical Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA. caiy1@wyeth.com
McConnell
Oliver
O
Bach
Alvin C
AC
D001274:Atmospheric Pressure; D055808:Drug Discovery; D005663:Furans / Q000737:chemistry*; D007477:Ions / Q000737:chemistry*; D013058:Mass Spectrometry / Q000191:economics / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis*; D010777:Photochemistry
D005663:Furans; D007477:Ions; D004364:Pharmaceutical Preparations; C018674:tetrahydrofuran