The formation of inactive, insoluble forms of peptide can be minimized or,
alternatively, inactive, insoluble forms of peptide compounds, if
present, can be converted into more physiologically active, soluble forms
by dissolving peptide samples in aqueous base and then acidifying the
aqueous mixture to precipitate the peptide in the presence of at least
one of a salt and a co-solvent. Preferably, both a salt and co-solvent
are present. By carrying out the precipitation relatively rapidly (at
least in a first stage of acidifying in which the pH of the alkaline
medium is reduced to a pH in the range of 6 to 7.5, after which
acidification to a final desired pH, e.g., 3 to 6, can occur more slowly)
at relatively low temperature, the dissolution characteristics of the
resultant precipitated peptide are even further improved. The process is
robust, consistent, and suitable for commercial scale manufacture of
peptides.