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Description of key information

GLP study according to EU Method A.6 and OECD Guideline for Testing of Chemicals No. 105 (Flask method).
General Physical Chemistry, Schering AG, Berlin, Study report No. NC34EY10 (APC 54/99), dated 1999-08-25.
Hydroxydrospirenone can be considered as insoluble in accordance with the descriptive term of DAB 10 and USP 23.

Key value for chemical safety assessment

Water solubility:
93 mg/L
at the temperature of:
20 °C

Additional information

Method:

A total of 4 test tubes each containing approx.10mg Hydroxydrospirenone and 5 mL water, respectively, are kept in a water bath while stirring at 30°C. After one day the temperature of the water bath is set to 20.0°C. Samples are taken during days 3, 4, 5 and 6 (calculated from the start at 20°C) about 2 mL of the suspension are drawn up with a pasteur pipette and centrifuged for 0.5 h at an acceleration of 30000 g for separation of undissolved substance from water using a ultracentrifuge with temperature control. The temperature during centrifugation is kept constant at 20°C by appropriate cooling of the rotor casing.

0.5 mL of the clear supernatant solution obtained from centrifugation is taken with a precision syringe, diluted with 0.5 mL acetonitrile and analyzed by HPLC. Each sample is injected twice. The pH values of the saturated water solutions are monitored with a calibrated glass electrode after adding a conducting salt (KCl). Each saturation experiment is made in duplicate.

At the last sampling time the insoluble residues from the saturated solutions in water are separated and dried on a clay disk. Because of the small amount of the insoluble residues both are combined before measurement. The insoluble residue and the starting material are analyzed by X-ray powder diffraction and the diffractograms are compared with each other.

Additionally the insoluble residue and the clear supernatant solutions from the last sampling time are investigated by HPLC

Results:

The actual concentrations are averaged after a saturation time of 3 days. The following solubility is obtained after equilibration at 20°C with 95% confidential interval:

                                                   S20= 93 mg/L ± 5 mg/L

The pH value is determined to be 5.4 (mean value of the pH values of the investigated samples). Hydroxydrospirenone can be considered as insoluble in accordance with the descriptive term of DAB 10 and USP 23.

 

The starting material and the residue show no differences in their X-ray powder diffractograms. It is no change in the solid state form of the insoluble residue from water with respect to the starting material.

The investigation of the insoluble residue by HPLC (100%-method) shows that the insoluble residue has a about 5 % higher purity than the starting material. In exchange in the clear water solutions the content of hydroxidrospirenone is only about 40%. This lets conclude a better solubility of the impurities in water.