The invention provides a purification and
ion control method of
teriparatide acetate. The method includes the steps of firstly, using the
acetonitrile system of a
ammonium bicarbonate aqueous solutionto perform first purification on a crude
peptide solution; secondly, using the
acetonitrile system of
sodium sulfate /
sulfuric acid to perform second purification on the collected eluent; thirdly, using the
acetonitrile system of an
ammonium acetate
aqueous solution to elute the collected eluent, and then using the acetonitrile system of an
acetic acid aqueous solution to elute the collected eluent to perform high performance
liquid phase salt conversion; fourthly, performing vacuum concentration on the eluent after the salt conversion, and then adding
hydrochloric acid. The method has the advantages that the
hydrochloric acid is added after multiple times of purification and salt conversion to perform acetate
plasma content control, different chromatographic systems are used, the purity of the
teriparatide acetate prepared by the large-scale preparation is larger than 99%,
methionine sulfoxide teriparatide impurity total sum is not larger than 0.05%, maximum unknown individual
impurity is not larger than 0.10%,
acetate ion content is not larger than 5%,
chlorine ion content is not larger than 4%, trifluoroacetate content and
sulfate content are not larger than 0.1%, and total yield is lager than 60%.