Androst-4-ene-3,17-dione

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 to 21 Nov 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Incubation time: 5 days

Buffers:

Buffer solutions:
- 0.05 M acetate buffer solution pH 4
- 0.05 M phosphate buffer solution pH 7
- 0.05 M borate buffer pH 9

Buffer solutions for calibration of pH meter and electrode:
- standard buffer solutions pH 4 (Art. 33543), pH 7 (Art. 33546), pH 9 (Art. 33548)

Details on test conditions:

- alliquots of test item filled into sterilized 5 ml autosampler vials, lightly closed with screw caps
- incubated at 50 +/- 0.1 °C in a thermostatic water bath for 5 days
- pH values measured at the start of incubation and at the end of hydrolysis experiment
- possible photolytic degradation was prevented by exclusion of light from the hydrolysis solutions by using a thermostatic bath made of stainless steel with metal cover
- after 5 days the samples were analyzed by HPLC

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

ca. 10 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

ca. 10 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

ca. 10 mg/L

Number of replicates:

The initial concentration was measured in triplicate.

Preliminary study:

No hydrolytic degradation was observed within 5 days at pH 4, 7 and 9 at 50 ± 0.1 °C.

Transformation products:

no

% Recovery:

100.4

pH:

4

Temp.:

50 °C

Duration:

5 d

% Recovery:

101

pH:

7

Temp.:

50 °C

Duration:

5 d

% Recovery:

99.9

pH:

9

Temp.:

50 °C

Duration:

5 d

Key result

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Remarks on result:

other: "considered to" be acc. to the EC-Test Guideline

Details on results:

The data show that at pH 4, 7 and 9 essentially no hydrolysis occured within 5 days at 50 +/- 0.1 °C. Therefore the test item is considered to be hydrolytically stable (t1/2 > 1 year at 25 °C) and no further testing is necessary.

Validity criteria for the hydrolysis study:

Target condition according to guideline:	Actual condition according to the study:	Validity criteria met:
The analytical method used will depend on the nature of the substance and must be sufficiently precise and sensitive to detect a reduction of 10 % of the initial concentration.	Analysis via HPLC is sensitive enough to detect a reduction of 10% of the initial concentration.	Yes
A sufficient number of samples (not less than four) should be chosen to cover the range 20 to 70 % of hydrolysis to test for pseudo-first order behaviour at the specified pH values.	pH 4 (50°C): 6 measurements pH 7 (50°C): 6 measurements pH 9 (50°C): 6 measurements	Yes
The temperature, pH value, buffer composition and a table of all concentration-time data points shall be stated.	The temperature, pH value, buffer composition and a table of all concentration-time data points is stated for each test.	Yes

Conclusions:

Androst-4-ene-3,17-dione can be considered to be hydrolytically stable at pH 4, 7 and 9 at 25 °C.

Executive summary:

The rate of hydrolysis of Androst-4-ene-3,17-dione in aqueous solution buffered to pH values of 4, 7 and 9 was studied according to EU testing guideline C.7. No hydrolytic degradation was observed within 5 days at pH 4, 7 and 9 at 50 ± 0.1 °C (pretest).

Description of key information

Androst-4-ene-3,17-dione can be considered to be hydrolytically stable at pH 4, 7 and 9 at 25 °C.

Additional information

No hydrolytic degradation was observed within 5 days at pH 4, 7 and 9 at 50 ± 0.1 °C (pretest). Therefore no further testing is required.