Separation of long oligonucleotides

A method for separation of analyzing encapsulated oligonucleotides or nucleic acid biopolymers, comprising:

• solubilizing a sample containing a plurality of encapsulated oligonucleotide species, the plurality of encapsulated oligonucleotide species including a first encapsulated oligonucleotide species containing a first oligonucleotide species and a second encapsulated oligonucleotide species containing a second oligonucleotide species, wherein solubilizing the sample includes releasing the first and second oligonucleotide species;
• loading the solubilized sample onto a column, the column includes a stationary phase including divinyl benzene or derivatives thereof;
• flowing a mobile phase consisting of a combination of a first solution and a second solution through the column to elute the first and second oligonucleotide species, the first solution including an ion pairing reagent, the ion pairing reagent including a primary amine or a secondary amine, wherein the proportion of the first solution and the second solution in the mobile phase is varied over time to separate the first oligonucleotide species from the second oligonucleotide species;
• and
• analyzing at least one of the first oligonucleotide species and the second oligonucleotide species using a mass spectrometer.

A method for separation of analyzing viral particles, comprising:

• solubilizing a sample containing a plurality of viral particle species, the plurality of viral particle species including a first viral particle species containing a first oligonucleotide species and a second viral particle species containing a second oligonucleotide species, wherein solubilizing the sample includes releasing the first and second oligonucleotide species;
• loading the solubilized sample onto a column, the column includes a stationary phase including divinyl benzene or derivatives thereof;
• flowing a mobile phase consisting of a combination of a first solution and a second solution through the column to elute the first and second oligonucleotide species, the first solution including an ion pairing reagent, the ion pairing reagent including a primary amine or a secondary amine, wherein the proportion of the first solution and the second solution in the mobile phase is varied over time to separate the first oligonucleotide species from the second oligonucleotide species;
• and
• analyzing at least one of the first oligonucleotide species and the second oligonucleotide species using a mass spectrometer.