Matrix‐assisted laser desorption/ionization Fourier‐transform mass spectrometry of oligodeoxyribonucleotides

Conditions for the matrix‐assisted laser desorption/ionization (MALDI) of oligodeoxyribonucleotides at 355 nm, developed using a 3‐Tesla Fourier‐transform ion cyclotron resonance mass spectrometer (FTMS), are reported. Efficient ion trapping and matrix selection are critical to the desorption and detection of oligonucleotides by FTMS. The achievable upper mass limit for the MALDI‐FTMS of bio molecules on our 3‐Tesla system has been extended from approximately 2 kDa to 6 kDa through the use of pulsed‐trapping‐plate ion deceleration techniques. By implementing the deceleration techniques, molecular ions for bovine insulin (MW = 5733.5), an oligodeoxythymidylic acid, pd[T]₁₀ (MW = 3060.0), and a mixed‐base 12‐mer (MW = 3611.5) have been measured. For the analysis of oligonucleotides by FTMS, selection of an appropriate MALDI matrix is essential for the generation of [MH]⁻ ions. 3‐Hydroxypicolinic acid provides a significant improvement over 2,5‐dihydroxybenzoic acid for production of deprotonated molecules particularly for mixed‐base oligomers. MALDI studies using FTMS have been duplicated using a newly constructed time‐of‐flight mass spectrometer (TOFMS) and oligonucleotide fragmentation on the TOFMS is reduced relative to that observed by FTMS. This may be a consequence of the longer times (milliseconds) required for FTMS detection.