Method for the purification of prostaglandins

1. A method for the purification of a prostaglandin by supercritical fluid chromatography, said method comprising using a stationary phase and a mobile phase comprising carbon dioxide, wherein the stationary phase is a non-chiral stationary phase selected from the group consisting of 4 ethyl pyridine, 2-ethyl pyridine and pyridine urea or a chiral stationary phase and the prostaglandin is a compound of formula (I), a compound of formula (II), or a compound of formula (IV):

wherein,

V is C;

W is

X is CONR 12 R 13 or CO 2 R 12 ;

Y is

Z is C 1-20 -alkyl, C 2-20 -alkynyl, —O—(C 6-20 -aryl) or —(C 1-20 -alkyl)-(C 5-20 -aryl), wherein the aryl group is optionally substituted with one to three substituents selected from the group consisting of C 1-20 -alkyl, halo and C(halo) 3 ;

R 1 and R 2 are independently H or OH, or R 1 and R 2 together form

R 3 and R 4 are independently H or OH;

R 5 and R 6 are independently H or OH, or R 5 and R 6 together form

R 7 and R 8 are independently H, OH, halo or C 1-20 -alkyl; R 9 and R 10 are independently H or C 1-20 -alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from CONR 12 R 13 , CO 2 R 12 , and CO 2 − -M + ; R 11 is C 1-20 -alkyl or —O—(C 1-20 -alkyl), wherein the alkyl group is optionally substituted with one or more substituents selected from CONR 12 R 13 , CO 2 R 12 , and CO 2 − -M + ; R 12 and R 13 are independently selected from the group consisting of H and C 1-20 alkyl; M + is a counter cation; and

Halo is fluorine, chlorine, bromine or iodine.

2. A method according to claim 1 , wherein the prostaglandin is selected from the group consisting of:

3. A method according to claim 1 , wherein the prostaglandin is:

4. A method according to claim 1 , wherein the stationary phase is a chiral stationary phase.

5. A method according to claim 4 , wherein the chiral stationary phase is an amylose or cellulose containing polymer which is coated or immobilized on silica.

6. A method according to claim 4 , wherein the chiral stationary phase is selected from the group consisting of cellulose-3,5-dimethylphenylcarbamate-on silica, amylose-(S)-alpha-methylbenzylcarbamate on silica, cellulose-3,5-dichlorophenylcarbamate on silica, amylose-3,5-dimethylphenylcarbamate on silica, cellulose-4-methylbenzoate on silica and cellulose-cinnamate on silica.

7. A method according to claim 1 , wherein the stationary phase is a non-chiral stationary phase selected from the group consisting of 4-ethyl pyridine, 2-ethyl pyridine and pyridine urea.

8. A method according to claim 1 , wherein the mobile phase further comprises at least one modifier.

9. A method according to claim 8 , wherein the at least one modifier is selected from the group consisting of at least one alcohol, acetonitrile, ethyl acetate, methylene chloride and a combination thereof.

10. A method according to claim 8 , wherein the at least one modifier includes an alcohol selected from the group consisting of methanol, ethanol, propanol, isopropanol and a combination thereof.

11. A method according to claim 8 , wherein the at least one modifier is present in a quantity from about 1% v/v to the carbon dioxide.

12. A method according to claim 8 , wherein the at least one modifier is present in a quantity from about 1% w/w to the carbon dioxide.

13. A method according to claim 8 , wherein the at least one modifier is present in a quantity from about 5% v/v to the carbon dioxide.

14. A method according to claim 8 , wherein the at least one modifier is present in a quantity from about 5% w/w to the carbon dioxide.

15. A method according to claim 1 , wherein the method provides a purified prostaglandin which is at least 99% chemically pure.

16. A method according to claim 1 , wherein the method provides a purified prostaglandin which is at least 99% isomerically pure.

17. A method for the purification of latanoprost by supercritical fluid chromatography, said method comprising the use of a chiral stationary phase and a mobile phase comprising carbon dioxide.

18. A method for purifying a crude prostaglandin, comprising injecting the crude prostaglandin onto a column comprising a stationary phase, eluting the crude prostaglandin through the column using a mobile phase comprising supercritical carbon dioxide, and collecting a fraction comprising a purified prostaglandin, wherein the stationary phase is a non-chiral stationary phase selected from the group consisting of 4-ethyl pyridine, 2-ethyl pyridine and pyridine urea or a chiral stationary phase and the prostaglandin is a compound of formula (I), a compound of formula (II), or a compound of formula (IV):

wherein,

V is C;

W is

X is CONR 12 R 13 or CO 2 R 12 ;

Y is

Z is C 1-20 -alkyl, C 2-20 -alkynyl, —O—(C 6-20 -aryl) or —(C 1-20 -alkyl)-(C 6-20 -aryl), wherein the aryl group is optionally substituted with one to three substituents selected from the group consisting of C 1-20 -alkyl, halo and C(halo) 3 ;

R 1 and R 2 are independently H or OH, or R 1 and R 2 together form

R 3 and R 4 are independently H or OH;

R 5 and R 6 are independently H or OH, or R 5 and R 6 together form

R 7 and R 8 are independently H, OH, halo or C 1-20 -alkyl;

R 9 and R 10 are independently H or C 1-20 -alkyl, wherein the alkyl group is optionally substituted with one or more substituents selected from CONR 12 R 13 , CO 2 R 12 , and CO 2 − M + ;

R 11 is C 1-20 -alkyl or —O—(C 1-20 -alkyl), wherein the alkyl group is optionally substituted with one or more substituents selected from CONR 12 R 13 , CO 2 R 12 , and CO 2 − -M + ;

R 12 and R 13 are independently selected from the group consisting of H and C 1-20 alkyl;

M + is a counter cation; and

Halo is fluorine, chlorine, bromine or iodine.