this invention provides novel approach that successfully address the issues associated with the reduced resolution , sensitivity and recovery in ion - exchange chromatography in handling certain types of analytes . the much improved and versatile approach entails the inclusion of one or more modifying agent in the mobile phase , and / or pre - treatment of the stationary phase with such modifying agents . ion - exchange hplc using such mobile phase or stationary phase displays much improved resolution and sensitivity as well as higher recovery rate . in certain preferred embodiments , for example , the use of the peg - modified mobile phase regimes when performing anion - exchange hplc analysis of pegylated oligonucleotide drug substance substantially increases analytical sensitivity for low levels of pegylated impurities . anion - exchange hplc is an often - used chromatographic mode for separation of oligonucleotides . when analytical parameters are optimized , single nucleotide variants ( e . g ., n − 1 , n + 1 ) are often chromatographically specified in the presence of longer (˜ 30 - 40 nt ) oligonucleotide sequences . for example , as shown in fig1 with the single nucleotide variants labeled , the uv detector trace ( at 259 nm ) displays a clean oligonucleotide separation . when separating pegylated oligonucleotides under similar analytical conditions , differences in the appearance of the chromatography are noted relative to that observed for the non - pegylated analogs . higher values relative to non - pegylated analogs for lower limits of detection ( lod ) and quantitation ( loq ) are often observed for pegylated oligonucleotides . reduced retention times and band broadening in the chromatographic trace are typically found . impurity peaks are observed with valleys and inflection points presenting with a more ‘ vague ’ appearance . peak resolution of the respective species is often much lower . the typical linear correlation of sample load on the column and uv detector response becomes quite poor when observing pegylated oligonucleotide analytes present at levels below about 1 % ( w / w ) of the nominal sample concentration . this non - linearity is due to poor analyte recovery at low on - column sample loads . the uv detector trace of a typical pegylated oligonucleotide separation is shown below in fig2 , with the single nucleotide variants labeled . when a series of standards are prepared consisting of the pegylated oligonucleotide at the method - defined concentration spiked with varying levels of an authentic length - based pegylated impurity , the injections indicate poor chromatographic recovery of the spiked species . unity extinction at the wavelength of detection was reasonably assumed for each species on a w / w basis . the peak signal - to - noise ( s / n ) values for the spiked impurity were calculated as the quotient of peak height and baseline noise ( peak - to - peak noise in a baseline region free from injection interference ), and the chromatographic recovery was calculated as the ratio of the impurity peak area % ( of total detector response due to sample load ) and the theoretical w / w % of the spiked material ( as - is weight basis ). because good chromatographic recoveries were consistently observed for samples with non - pegylated impurities spiked into non - pegylated oligonucleotide sample solutions , it was assumed that the observed poor recovery with pegtlated oligonucleotide sample solutions was due to the presence of the peg moiety associated with the analytes . without wishing to be bound , an interpretation of the observed poor recovery is based on the presence of the peg moiety associated with the analytes . in addition to interfering with the counter - ionic interactions of the column phase and the negatively charged oligonucleotide backbone , the peg may also interact with the surface of the hydrophobic polymeric phase support of the non - porous beads . if the analytes display affinity , a portion of the sample load will adsorb on these surfaces and fail to fully partition along the chemical phase . the dispersed adsorbed analyte may then just ‘ bleed ’ off the column and never appear as a peak in the detector trace , effectively compromising the observed chromatographic recovery . it was considered that the adsorption of the analyte on the column support beads may be limited , and that saturating the sites with a suitable proxy might allow the sample load to proceed unheeded across the column chemistry . in one aspect , the invention generally relates to a method for analyzing or purifying one or more ionic analytes in a sample by anion - exchange chromatography . the method includes : providing an anion - exchange column packed with an anion - exchange stationary phase ; providing an anion - exchange mobile phase having a modifying agent ; performing anion - exchange chromatography under a condition allowing anion exchange between the one or more ionic analytes in the sample and the anion - exchange stationary phase , thereby separating the one or more ionic analytes in the anion - exchange column ; and analyzing and / or collecting the separated one or more ionic analytes . the condition under which the anion - exchange chromatography is performed is dependent on the applicant at hand , the nature and amount of the analyte ( s ) and the modifying agents employed , as well as whether it is analytical or preparative chromatography . guided by the present disclosure , one of ordinary skill in the art will be able to identify the condition ( s ) under which to perform the chromatography . the analytes may be any components ( including impurities ), for example , nucleic acids ( e . g ., oligonucleotides , oligonucleosides , aptamers ), peptides ( e . g ., proteins , polypeptides , antibodies , antibody fragments ), polysaccharides ( e . g ., arabinoxylans , celluloses , chitins , pectins ), lipids ( e . g ., fats , sterols , monoglycerides , diglycerides , triglycerides , phospholipids ), metabolites ( e . g ., primary metabolites , secondary metabolites ), and natural products ( e . g ., extracted from terrestrial plants , marine organisms , microorganism fermentation broths ). these analytes may or may not be conjugated with one or more moieties , such as polyol , polyethylene - glycol ( i . e ., pegylated ), etc . compounds and components that may be found in samples suitable for analysis by the methods disclosed herein include , for example , compounds that are conjugated with one or more of poly ( urethanes ), poly ( siloxanes ), poly ( methyl methacrylate ), poly ( vinyl alcohol ), poly ( ethylene ), poly ( vinyl pyrrolidone ). non - limiting examples include poly ( 2 - hydroxy ethyl methacrylate ), poly ( n - vinyl pyrrolidone ), poly ( methyl methacrylate ), poly ( vinyl alcohol ), poly ( acrylic acid ), polyacrylamide , poly ( ethylene - co - vinyl acetate ), poly ( ethylene glycol ), poly ( methacrylic acid ), polylactides , polyglycolides , poly - l - glutamic acid , poly ( lactide - co - glycolides ), polyanhydrides , polyorthoesters . in certain embodiments , at least one of the one or more ionic analytes includes a compound comprising a polyethylene - glycol moiety . in certain embodiments , at least one of the one or more ionic analytes comprises a polyethylene glycol - conjugated oligonucleotide / polypeptide . in certain embodiments , the polyethylene glycol - conjugated oligonucleotide / polypeptide includes from about 3 k da to about 100 k da of polyethylene oxide ( e . g ., from about 3 k da to about 100 k da , from about 3 k da to about 75 k da , from about 3 k da to about 50 k da , from about 3 k da to about 30 k da , from about 3 k da to about 20 k da , from about 3 k da to about 10 k da , from about 5 k da to about 100 k da , from about 10 k da to about 100 k da , from about 10 k da to about 100 k da , from about 30 k da to about 100 k da , from about 50 k da to about 100 k da ). in certain embodiments , the polyethylene glycol - conjugated oligonucleotide includes from about 5 to about 2 , 000 units of nucleotides ( e . g ., from about 5 to about 2 , 000 units , from about 5 to about 1 , 500 units , from about 5 to about 1 , 000 units , from about 5 to about 500 units , from about 5 to about 200 units , from about 5 to about 100 units , from about 5 to about 50 units , from about 10 to about 2 , 000 units , from about 50 to about 2 , 000 units , from about 100 to about 2 , 000 units , from about 500 to about 2 , 000 units , from about 1 , 000 to about 2 , 000 units , from about 1 , 500 to about 2 , 000 units ). an analyte may be present at any suitable concentration , for example , at a concentration from about 0 . 05 μm to about 500 μm ( e . g ., from about 0 . 05 μm to about 400 μm , from about 0 . 05 μm to about 300 μm , from about 0 . 05 μm to about 200 μm , from about 0 . 05 μm to about 100 μm , from about 0 . 05 μm to about 50 μm , from about 0 . 05 μm to about 30 μm , from about 0 . 05 μm to about 20 μm , from about 0 . 05 μm to about 10 μm , from about 0 . 05 μm to about 5 μm , from about 0 . 05 μm to about 3 μm , from about 0 . 05 μm to about 2 μm , from about 0 . 05 μm to about 1 μm , from about 0 . 05 μm to about 0 . 5 μm , from about 0 . 1 μm to about 500 μm , from about 0 . 5 μm to about 500 μm , from about 1 μm to about 500 μm , from about 2 1 lim to about 500 μm , from about 5 μm to about 500 μm , from about 10 μm to about 500 μm , from about 20 μm to about 500 μm , from about 30 μm to about 500 μm , from about 50 μm to about 500 μm , from about 100 μm to about 500 μm ). depending on the analytes , modifying agents suitable for use in the disclosed methods may be selected , for example , among poly ( urethanes ), poly ( siloxanes ), poly ( methyl methacrylate ), poly ( vinyl alcohol ), poly ( ethylene ), poly ( vinyl pyrrolidone ). non - limiting examples include poly ( 2 - hydroxy ethyl methacrylate ), poly ( n - vinyl pyrrolidone ), poly ( methyl methacrylate ), poly ( vinyl alcohol ), poly ( acrylic acid )., polyacrylamide , poly ( ethylene - co - vinyl acetate ), poly ( ethylene glycol ), poly ( methacrylic acid ), polylactides , polyglycolides , poly - l - glutamic acid , poly ( lactide - co - glycolides ), polyanhydrides , polyorthoesters . in certain embodiments , the modifying agent is an organic compound having at least three units of moiety wherein the moiety is independently selected from c — o — c moiety or — oh group . in certain embodiments , the modifying agent includes a polyol moiety . in certain embodiments , the modifying agent includes an oligomeric alkylene oxide moiety . in certain embodiments , the modifying agent is an alkylene oxide oligomer . in certain embodiments , the alkylene oxide oligomer is an ethylene oxide oligomer . the ethylene oxide oligomer may include any suitable molecular weight , for example , from about 3 k da to about 100 k da ( e . g ., from about 3 k da to about 100 k da , from about 3 k da to about 75 k da , from about 3 k da to about 50 k da , from about 3 k da to about 30 k da , from about 3 k da to about 20 k da , from about 3 k da to about 10 k da , from about 5 k da to about 100 k da , from about 10 k da to about 100 k da , from about 10 k da to about 100 k da , from about 30 k da to about 100 k da , from about 50 k da to about 100 k da ). the modifying agent may be present in the anion - exchange mobile phase at any suitable concentration , for example , from about 0 . 1 μm to about 100 μm ( e . g ., from about 0 . 1 μm to about 50 μm , from about 0 . 1 μm to about 30 μm , from about 0 . 1 μm to about 20 μm , from about 0 . 1 μm to about 10 μm , from about 0 . 1 μm to about 5 μm , from about 0 . 1 μm to about 3 μm , from about 0 . 1 μm to about 2 μm , from about 0 . 1 μm to about 1 μm , from about 0 . 5 μm to about 100 μm , 1 μm to about 100 μm , 2 μm to about 100 μm , 5 μm to about 100 μm , 10 μm to about 100 μm , 20 μm to about 100 μm , 30 μm to about 100 μm , 50 μm to about 100 μm ). the sensitivity of anion - exchange chromatography using the anion - exchange mobile phase with the modifying agent is greater than , for example at least 2 fold greater than , that of anion - exchange chromatography using the same anion - exchange mobile phase without the modifying agent . in certain embodiments , the sensitivity of anion - exchange chromatography using the anion - exchange mobile phase with the modifying agent is at least 3 fold greater than , preferably at least 5 fold greater than , that of anion - exchange chromatography using the same anion - exchange mobile phase without the modifying agent . in certain embodiments , the sensitivity of anion - exchange chromatography using the anion - exchange mobile phase with the modifying agent is at least 10 fold greater than that of anion - exchange chromatography using the same anion - exchange mobile phase without the modifying agent . in another aspect , the invention generally relates to a method for performing anion - exchange chromatography . the method includes adding a modifying agent to a mobile phase prior to performing anion - exchange , wherein the modifying agent is an organic compound comprising at least three units of moiety , wherein the moiety is independently selected from c — o — c moiety or — oh group . in yet another aspect , the invention generally relates to a method for performing ion - exchange chromatography of a sample comprising an ionic analyte . the method includes adding as an additive a modifying agent to a mobile phase prior to performing ion - exchange chromatography using the mobile phase . in certain embodiments , the ion - exchange chromatography is performed under anion - exchange mode . in certain embodiments , the ionic analyte includes a polyethylene glycol - conjugated polypeptide or oligonucleotide . in certain embodiments , the ion - exchange chromatography is performed under cation - exchange mode . in certain embodiments , the ionic analyte includes a polyethylene glycol - conjugated oligonucleotide or polypeptide . unity extinction at the wavelength of detection was reasonably assumed for each species on a w / w basis . the peak signal - to - noise ( s / n ) values for the spiked impurity were calculated as the quotient of peak height and baseline noise ( peak - to - peak noise in a baseline region free from injection interference ), and the chromatographic recovery was calculated as the ratio of the impurity peak area % ( of total detector response due to sample load ) and the theoretical w / w % of the spiked material ( as - is weight basis ). the use of non - functionalized polyethylene glycol with average molar mass of 40k da was evaluated as a mobile phase additive / modifier . when the peg was incorporated into the mobile phase at levels of 0 . 10 - 0 . 15 mg / ml ( 2 . 5 - 3 . 9 μm ), the detection of low levels of pegylated oligonucleotide drug substance impurities was enabled and & gt ; 90 % chromatographic recovery was observed in those samples spiked with known amounts of authentic impurities . the experimental results were corroborated over three different anion exchange hplc analysis methods applicable to three different pegylated oligonucleotide drug substances . the evaluations were limited to those analytical columns using pellicular anion exchange resin consisting of quaternary amine functionality and a nonporous polymeric substrate , specifically the dionex dnapac pa100 and pa200 models . fig3 shows exemplary anion - exchange hplc of very dilute solutions of pegylated oligonucleotide drug substance by original analysis conditions . the stacked plots ( uv trace at 258 nm ) represent six overlaid chromatograms of solutions ranging from 0 . 04 μm to 0 . 2 μm drug substance . a signal ( at 14 . 5 min ) was observed for only the most concentrated of the solutions . fig4 shows exemplary anion - exchange hplc of the same solutions under identical analysis conditions but with utilization of the mobile phase modifying agent . in this specification and the appended claims , the singular forms “ a ,” “ an ,” and “ the ” include plural reference , unless the context clearly dictates otherwise . unless defined otherwise , all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art . although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure , the preferred methods and materials are now described . methods recited herein may be carried out in any order that is logically possible , in addition to a particular order disclosed . references and citations to other documents , such as patents , patent applications , patent publications , journals , books , papers , web contents , have been made in this disclosure . all such documents are hereby incorporated herein by reference in their entirety for all purposes . any material , or portion thereof , that is said to be incorporated by reference herein , but which conflicts with existing definitions , statements , or other disclosure material explicitly set forth herein is only incorporated to the extent that no conflict arises between that incorporated material and the present disclosure material . in the event of a conflict , the conflict is to be resolved in favor of the present disclosure as the preferred disclosure . the representative examples disclosed herein are intended to help illustrate the invention , and are not intended to , nor should they be construed to , limit the scope of the invention . indeed , various modifications of the invention and many further embodiments thereof , in addition to those shown and described herein , will become apparent to those skilled in the art from the full contents of this document , including the examples which follow and the references to the scientific and patent literature cited herein . the following examples contain important additional information , exemplification and guidance that can be adapted to the practice of this invention in its various embodiments and equivalents thereof .