Ultra-pure agonists of guanylate cyclase C, method of making and using same

1. A purified peptide comprising the Guanylate Cyclase-C(GCC) agonist sequence of SEQ ID NO: 9, wherein the purified peptide has the following characteristics:

a) has a bulk density of not greater than 0.1 g/mL;

b) contains less than 50 ppm acetamide; and

c) less than 0.05% trifluoroacetic acid (TFA) per total weight of the peptide.

2. The purified peptide of claim 1 , wherein the peptide is stable at 25° C. for at least three months.

3. The purified peptide of claim 1 , wherein the peptide has a particle size distribution characterized by:

a) a D10 value of between about 2-15 μm;

b) a D50 value of between about 15-50 μm; and

c) a D90 value of between about 40-80 μm,

when measured by light scattering with liquid dispersant.

4. The purified peptide of claim 1 , wherein the peptide has a bulk density of not greater than 0.06 g/mL.

5. The purified peptide of claim 1 , wherein the peptide has a chromatographic purity of no less than 97%.

6. The purified peptide of claim 1 , wherein the water content of the peptide is less than 10% of the total weight of the peptide.

7. The purified peptide of claim 1 , wherein the peptide contains less than 0.5% per weight of the peptide of one or more impurities selected from the group consisting of acetonitrile, alcohols, ammonium, and acetate.

8. The purified peptide of claim 7 , wherein the peptide contains less than 300 ppm acetonitrile.

9. The purified peptide of claim 7 , wherein the peptide contains less than 1000 ppm isopropanol.

10. The purified peptide of claim 7 , wherein the peptide contains less than 600 ppm isopropanol.

11. The purified peptide of claim 7 , wherein the acetate content of the peptide is less than 0.25% of the total weight of the peptide.

12. The purified peptide of claim 1 , wherein the topoisomer content of the peptide is less than 2% of the total weight of the peptide.