In this webinar we will present direct, robust and easy-to-use techniques to fully characterize the nucleotide sequence of highly modified single-stranded RNAs by top down tandem MS. This will include a case study for a N-acetylgalactosamine modified RNA sense strand. The approach can be applied on a single strand level, as well as on siRNA duplex level in a single electrospray ionization MS (ESI-MS) experiment. This procedure also allows us to reliably predict the structure of impurities that can occur during oligonucleotide production, which supports process improvements in manufacturing.