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Estimation of hydrolytic stability on basis of the hydrolytic behavior of structurally similar compounds.
General Physical Chemistry, Schering AG, Berlin. Study report A02701 (APC 228/00), dated 2000-11-27.
Hydroxydrospirenone can be expected to be hydrolytic stable at pH4 and to hydrolyse with half-lives of approx. 340h at pH7 or 78h at pH9.

Key value for chemical safety assessment

Additional information

Hydroxydrospirenone (5-Hydroxy-6 beta,7 beta;15 beta,16 beta-dimethylene-3-oxo-5 beta,17 alpha -pregnane-21,17-carbolactone) is the precursor compound of the very similar drospirenon (6 beta,7 beta;15 beta,16 beta-Dimethylene-3-oxo -17 alpha-pregn-4-ene -21,17-carbolactone). The only difference is that there is a double bond between positions 4 and 5 instead of the hydroxy group in position 5. The only reaction center, which could be susceptible to hydrolytic reactions, is the lactone ring attached at posion 17. This center is far away from the structural differences.

Therefore, the hydrolytic behavior of Hydroxydrospirenone is expected to be very similar to that of Drospirenon:

Drospirenon can hydrolyse at the lactone ring and simultaneously isomerize in position 17 (stereochemistry). The half-lives of these reactions in dependence on pH at 25°C are:

pH

half-life

(isomerization)

half-life

(hydrolysis)

4

7

9

12.3 d

12.8 d

-**

stable*

343 d

77.7 h

* less than 4% degradation within 50 days

** no equilibrium can be reached, due to fast hydrolysis