Peripheral opioid receptor antagonists and uses thereof

1. A packaged composition comprising a liquid composition comprising a compound of formula III:

wherein A − is a suitable anion; wherein the packaged composition is substantially free of tungsten; and wherein the liquid composition comprises less than about 190 ppm of a compound of formula II:

wherein X − is a suitable anion.

2. The packaged composition according to claim 1 , wherein the liquid composition comprises less than about 190 ppm total of the compound of formula II and a compound of formula IV:

wherein: R 1 and R 2 are each independently C 1-6 aliphatic; and

X − is a suitable anion.

3. The packaged composition of claim 1 , wherein the packaged composition comprises a syringe, a vial, a sachet or an ampoule.

4. A packaged composition comprising a liquid composition comprising a compound of formula III-1:

wherein the liquid composition comprises less than about 190 ppm of a compound of formula II-1:

5. The packaged composition of claim 4 , wherein the packaged composition comprises a syringe, a vial, a sachet or an ampoule.

6. The packaged composition according to claim 4 , comprising less than about 190 ppm total of the compound of formula II-1 and a compound of formula IV-1:

7. The packaged composition according to claim 1 , comprising 8 mg of a compound of formula III-1:

in 0.4 mL water, and a compound of formula II-1:

wherein the compound of formula II-1 is present in an amount of less than about 190 ppm.

8. The packaged composition according to claim 7 , wherein the liquid composition further comprises 2.6 mg sodium chloride, 0.16 mg edetate calcium disodium, and 0.12 mg glycine hydrochloride.

9. The packaged composition according to claim 1 , comprising 12 mg of a compound of formula III-1:

in 0.6 mL water, and a compound of formula II-1:

wherein the compound of formula II-1 is present in an amount of less than about 190 ppm.

10. The packaged composition according to claim 9 , wherein the liquid composition further comprises 3.9 mg sodium chloride, 0.24 mg edetate calcium disodium, and 0.18 mg glycine hydrochloride.

11. A method comprising the steps of: (i) providing a packaged composition, substantially free from tungsten, comprising a unit dosage of a liquid composition comprising 8 mg or 12 mg of a compound of formula III-1:

in 0.4 mL or 0.6 mL water, and a compound of formula II-1:

wherein the compound of formula II-1 is present in an amount of less than about 190 ppm; and (ii) administering the unit dosage to a subject via subcutaneous injection.

12. The method of claim 11 , wherein the packaged composition comprises a syringe, a vial, a sachet or an ampoule.

13. The method according to claim 11 , wherein the subject is suffering from opioid induced constipation.

14. The method according to claim 11 , wherein the tungsten is present in an amount of less than 50 parts per billion.

15. The method according to claim 11 , wherein the tungsten is present in an amount of less than 12 parts per billion.

16. The method according to claim 11 , wherein the liquid composition further comprises edetate calcium disodium and glycine hydrochloride.

17. The packaged composition of any one of claims 4 - 6 , wherein the packaged composition is substantially free of tungsten.

18. The packaged composition of claim 1 , wherein the liquid composition comprises less than about 187 ppm of the compound of formula II.

19. The packaged composition of claim 2 , wherein the liquid composition comprises less than about 187 ppm total of the compound of formula II and the compound of formula IV.

20. The packaged composition of claim 4 , wherein the liquid composition comprises less than about 187 ppm of the compound of formula II-1.

21. The packaged composition of claim 6 , comprising less than about 187 ppm total of the compound of formula II-1 and the compound of formula IV-1.

22. The packaged composition of claim 7 , wherein the compound of formula II-1 is present in an amount of less than about 187 ppm.

23. The packaged composition of claim 9 , wherein the compound of formula II-1 is present in an amount of less than about 187 ppm.

24. The method of claim 11 , wherein the compound of formula II-1 is present in an amount of less than about 187 ppm.

25. The packaged composition of claim 1 or 4 , wherein the packaged composition comprises a syringe.

26. The method of claim 11 , wherein the packaged composition comprises a syringe.

27. The packaged composition of claim 1 , wherein the liquid composition comprises less than about 185 ppm of the compound of formula II.

28. The packaged composition of claim 1 , wherein the liquid composition comprises less than about 150 ppm of the compound of formula II.

29. The packaged composition of claim 1 , wherein the liquid composition comprises less than about 125 ppm of the compound of formula II.

30. The packaged composition of claim 1 , wherein the liquid composition comprises less than about 100 ppm of the compound of formula II.

31. The packaged composition of claim 1 , wherein the liquid composition comprises less than about 25 ppm of the compound of formula II.

32. The packaged composition of claim 2 , wherein the liquid composition comprises less than about 185 ppm total of the compound of formula II and the compound of formula IV.

33. The packaged composition of claim 2 , wherein the liquid composition comprises less than about 150 ppm total of the compound of formula II and the compound of formula IV.

34. The packaged composition of claim 2 , wherein the liquid composition comprises less than about 125 ppm total of the compound of formula II and the compound of formula IV.

35. The packaged composition of claim 2 , wherein the liquid composition comprises less than about 100 ppm total of the compound of formula II and the compound of formula IV.

36. The packaged composition of claim 2 , wherein the liquid composition comprises less than about 25 ppm total of the compound of formula II and the compound of formula IV.

37. The packaged composition of claim 4 , wherein the liquid composition comprises less than about 185 ppm of the compound of formula II-1.

38. The packaged composition of claim 4 , wherein the liquid composition comprises less than about 150 ppm of the compound of formula II-1.

39. The packaged composition of claim 4 , wherein the liquid composition comprises less than about 125 ppm of the compound of formula II-1.

40. The packaged composition of claim 4 , wherein the liquid composition comprises less than about 100 ppm of the compound of formula II-1.

41. The packaged composition of claim 4 , wherein the liquid composition comprises less than about 25 ppm of the compound of formula II-1.

42. The packaged composition of claim 6 , comprising less than about 185 ppm total of the compound of formula II- 1 and the compound of formula IV-1.

43. The packaged composition of claim 6 , comprising less than about 150 ppm total of the compound of formula II-1 and the compound of formula IV-1.

44. The packaged composition of claim 6 , comprising less than about 125 ppm total of the compound of formula II-1 and the compound of formula IV-1.

45. The packaged composition of claim 6 , comprising less than about 100 ppm total of the compound of formula II-1 and the compound of formula IV-1.

46. The packaged composition of claim 6 , comprising less than about 25 ppm total of the compound of formula II-1 and the compound of formula IV-1.

47. The packaged composition of claim 7 , wherein the compound of formula II-1 is present in an amount of less than about 185 ppm.

48. The packaged composition of claim 7 , wherein the compound of formula II-1 is present in an amount of less than about 150 ppm.

49. The packaged composition of claim 7 , wherein the compound of formula II-1 is present in an amount of less than about 125 ppm.

50. The packaged composition of claim 7 , wherein the compound of formula II-1 is present in an amount of less than about 100 ppm.

51. The packaged composition of claim 7 , wherein the compound of formula II-1 is present in an amount of less than about 25 ppm.

52. The packaged composition of claim 9 , wherein the compound of formula II-1 is present in an amount of less than about 185 ppm.

53. The packaged composition of claim 9 , wherein the compound of formula II-1 is present in an amount of less than about 150 ppm.

54. The packaged composition of claim 9 , wherein the compound of formula II-1 is present in an amount of less than about 125 ppm.

55. The packaged composition of claim 9 , wherein the compound of formula II-1 is present in an amount of less than about 100 ppm.

56. The packaged composition of claim 9 , wherein the compound of formula II-1 is present in an amount of less than about 25 ppm.

57. The method of claim 11 , wherein the compound of formula II-1 is present in an amount of less than about 185 ppm.

58. The method of claim 11 , wherein the compound of formula II-1 is present in an amount of less than about 150 ppm.

59. The method of claim 11 , wherein the compound of formula II-1 is present in an amount of less than about 125 ppm.

60. The method of claim 11 , wherein the compound of formula II-1 is present in an amount of less than about 100 ppm.

61. The method of claim 11 , wherein the compound of formula II-1 is present in an amount of less than about 25 ppm.