Aspects of the disclosure include methods for the preparation of a polynucleotide. In some embodiments, the method includes contacting a first polynucleotide composition including: a polynucleotide having a sequence of 7 or more nucleoside subunits and at least two of the nucleoside subunits are joined by a N3'→P5' thiophosphoramidate inter-subunit linkage； and non-target synthetic products and reagents； with a multivalent cation salt to precipitate a polynucleotide salt including at least one multivalent cation counterion； and separating the polynucleotide salt from the contacted first polynucleotide composition to produce a second polynucleotide composition including the polynucleotide salt. In certain embodiments, the method further includes contacting the polynucleotide salt with a reverse phase chromatography support； and eluting from the chromatography support a third polynucleotide composition including the polynucleotide. Also provided are compositions including a salt of the polynucleotide including at least one multivalent cation counterion.本發明之諸多態樣包括製備聚核苷酸之方法。在一些實施例中，該方法包括使第一聚核苷酸組合物與多價陽離子鹽接觸以使包括至少一個多價陽離子相對離子之聚核苷酸鹽沈澱，該第一聚核苷酸組合物包括：聚核苷酸，其具有7個以上核苷亞單元之序列且該等核苷亞單元中有至少兩個係由N3'→P5'硫代磷醯胺酯亞單元間鍵聯接合；以及非目標合成產物及試劑；及分離該聚核苷酸鹽與該經接觸之第一聚核苷酸組合物，以產生包括該聚核苷酸鹽之第二聚核苷酸組合物。在某些實施例中，該方法進一步包括使該聚核苷酸鹽與逆相層析載體接觸；及自該層析載體溶離包括該聚核苷酸之第三聚核苷酸組合物。亦提供包括該聚核苷酸之鹽的組合物，該聚核苷酸之鹽包括至少一個多價陽離子相對離子。
