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The hydrolytic stability of hydrocortisone-21-acetate was estimated on basis of the hydrolytic behaviour of a structurally similar compound.
Analytical Development Physical Chemistry, Schering AG, Berlin. Study report A08865 (ADP 2002_125), author M. Tschampel, dated 2002-06-18.
Result: Hydrocortisone-21-acetate can be expected to be hydrolytically stable at pH4 and to hydrolyze with half-lives of in the range of 50 to 120 d at pH 7 and in the range of 34 to 42 days at pH 9 (at 25°C).

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Additional information

The only hydrolyzable functional group in hydrocortisone-21-acetate is the ester function in the side chain at position17. The hydrolytic behaviour is expected to be similar to that of the structurally closely related compounds 21-Acetoxy-6 beta-fluoro-16 alpha-methyl -4-pregnene-3,20-dione / 21-Acetoxy-6 alpha-fluoro-16 alpha-methyl -4-pregnene-3,20-dione, which differ slightly in the steroid moiety, only.   The rate of hydrolysis of of these compounds was determined according to EC guideline C.7 at pH 4, 7 and 9. This compounds were found to be hydrolytically stable at pH 4 and to hydrolyze with half-lives of in the range of 50 to 120 days at pH 7 and in the range of 34 to 42 days at pH 9 (at 25°C), see following table:

pH

isomer

half-life

 

 

95 % confidence intervals for half-life

 

4

6-a

stable*

-

4

6-ß

stable*

-

7

6-a

109 d

101 – 118 d

7

6-ß

57 d

52 – 62 d

9

6-a

39.6 h

37.9 – 41.5 h

9

6-ß

36.8 h

34.7 – 39.1 h

* criterion according to EC testing guideline C.7: half-life > 1 year at 25 °C

Comparable results are to be expected for hydrocortisone-21-acetate.