Reaction mass of (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl]butanamide and (2S)-2-[(4S)-2-oxo-4-propylpyrrolidin-1-yl]butanamide

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 September 2006 - 6 October 2006

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 (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: 0, 2.4, 24, 120 h

Buffers:

- pH: 4
- Composition of buffer: Potassium hydrogen phthalate (0.05 M)

- pH: 7
- Composition of buffer: Disodium hydrogen orthophosphate (anhydrous) (0.03 M), Potassium dihydrogen orthophosphate (0.02 M) and Sodium chloride (0.02 M)

- pH: 9
- Composition of buffer: Disodium tetraborate (0.01 M) and Sodium chloride (0.02 M)

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: stoppered glass flasks
- Sterilisation method: filtration through a 0.2 μm membrane filter
- Lighting: The solutions were shielded from light whilst maintained at the test temperature.
- Measures taken to avoid photolytic effects: The solutions were shielded from light whilst maintained at the test temperature.
- Measures to exclude oxygen: ultrasonication and degassing with nitrogen
- If no traps were used, is the test system closed/open : closed
- Is there any indication of the test material adsorbing to the walls of the test apparatus? No

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

1 g/L

Duration:

120 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

1 g/L

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

1 g/L

Number of replicates:

2

Positive controls:

no

Negative controls:

no

Test performance:

The linearity of the detector response with respect to concentration was assessed for all three sample pH matrices over the nominal concentration range of 0 to 400 mg/l. These were satisfactory with a correlation coefficient of 1.000 being obtained in each case.

Transformation products:

not measured

Details on hydrolysis and appearance of transformation product(s):

Not measured.

% Recovery:

100

pH:

4

Temp.:

50 °C

Duration:

120 h

% Recovery:

100

pH:

7

Temp.:

50 °C

Duration:

120 h

% Recovery:

95

pH:

9

Temp.:

50 °C

Duration:

120 h

Key result

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Key result

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Key result

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes

Validity criteria fulfilled:

yes

Conclusions:

Based on a degradation study performed ccording to EC guidance and GLP principles, the estimated half-life at 25°C of the test substance is >1 year at pH 4, 7 and 9.

Description of key information

Based on a degradation study performed ccording to EC guidance and GLP principles, the estimated half-life at 25°C of the test substance is >1 year at pH 4, 7 and 9.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C