3,4‐Diaminobenzophenone Matrix for Analysis of Oligonucleotides by MALDI‐TOF Mass Spectrometry

Abstract This unit contains procedures for analysis of oligonucleotides by matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) mass spectrometry with 3,4‐diaminobenzophenone (DABP) as a matrix. This new matrix has demonstrated advantages in the analysis of oligonucleotides. With DABP as a matrix, intact oligonucleotide ions can be readily produced with lower laser powers, resulting in better detection limits, less fragmentation, and fewer alkali‐metal ion adducts compared with results obtained using conventional matrices. Minimal fragmentation and fewer alkali‐metal ion adducts were seen even at low oligonucleotide concentrations. It was also found that samples prepared with DABP are highly homogenous, therefore reducing the need to find “sweet spots” in MALDI. Finally, excellent shot‐to‐shot reproducibility, resolution, and signal‐to‐noise ratio are observed using the DABP matrix. Curr. Protoc. Nucleic Acid Chem . 31:10.12.1‐10.12.6. © 2007 by John Wiley & Sons, Inc.