provided is a method comprising introducing a sample comprising a plurality of oligonucleotides into an ion pair high performance liquid chromatography column having a buffered mobile phase and allowing at least a portion of the oligonucleotides to separate ; allowing the oligonucleotides to elute from the column ; and introducing the oligonucleotides into a mass spectrometer and quantifying at least a portion of the oligonucleotides by mass spectrometry . in the method , at least a portion of the oligonucleotides are co - eluting oligonucleotides that differ in mass by no more than 20 %; and the buffered mobile phase causes at least 50 mole percent of co - eluting oligonucleotides to have the same charge when they enter the mass spectrometer .