LPIT-ESI-MS Data for Nucleic Acids, SNP, and Therapeutic Oligonucleotides

We introduce a liquid-phase ion trap (LPIT) system that overcomes these limitations. It is discovered that the strong electric field within the LPIT effectively dissociates metal cation adducts from nucleic acids in seconds. The desalted nucleic acid ions are then immediately accumulated, enabling direct electrospray ionization (ESI)-MS analysis with a greater than 100-fold enhancement in signal intensity. Several demanding applications were then carried out, including resolving single-nucleotide polymorphisms with minimal A-T mass differences; directly analyzing PCR products for influenza subtyping without single-base extension; and precisely identifying a single phosphorothioate-to-phosphodiester substitution impurity in therapeutic oligonucleotides. This work demonstrates LPIT-ESI-MS as a robust and versatile platform for the rapid, direct, and high-fidelity analysis of nucleic acids.