A new matrix framework is presented
in this study for the improved
ionization efficiency of complex mixtures by matrix-assisted laser
desorption ionization (MALDI) mass spectrometry/imaging. Five nitro
indole (NI) derivatives [3-methyl-4-nitro-1H-indole (3,4-MNI), 3-methyl-6-nitro-1H-indole
(3,6-MNI), 2,3-dimethyl-4-nitro-1H-indole (2,3,4-DMNI), 2,3-dimethyl-6-nitro-1H-indole
(2,3,6-DMNI), and 4-nitro-1H-indole (4-NI)] were synthesized and shown
to produce both positive and negative ions with a broad class of analytes
as MALDI matrices. NI matrices were compared to several common matrices,
such as 2,5-dihydroxybenzoic acid (DHB), alpha-cyano-4-hydroxylcinnamic
acid (CHCA), sinapinic acid (SA), 1,5-diaminonaphthelene (1,5-DAN),
and 9-aminoacridine (9-AA), for the analysis of lipid, peptide, protein,
glycan, and perfluorooctanesulfonic acid (PFOS) compounds. 3,4-MNI
demonstrated the best performance among the NI matrices. This matrix
resulted in reduced ion suppression and better detection sensitivity
for complex mixtures, for example, egg lipids/milk proteins/PFOS in
tap water, while 2,3,6-DMNI was the best matrix for blueberry tissue
imaging. Several important aspects of this work are reported: (1)
dual-polarity ion production with NI matrices and complex mixtures;
(2) quantitative analysis of PFOS with a LOQ of 0.5 ppb in tap water
and 0.05 ppb in MQ water (without solid phase extraction enrichment),
with accuracy and precision within 5%; (3) MALDI imaging with 2,3,6-DMNI
as a matrix for plant metabolite/lipid identification with ionization
enhancement in the negative ion mode m/z 600–900 region; and (4) development of a thin film deposition
under/above tissue method for MALDI imaging with a vacuum sublimation
matrix on a high-vacuum MALDI instrument.