5-fluoro-2-methoxypyrimidin-4(3H)-one

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 November 2005 to 24 November 2005

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)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: A sample of the prepared solution was analysed in duplicate after a 500-fold dilution in mobile phase in order to determine the initial concentration of the test material. Following heating, the concentration of the test material in the solution was determined in duplicate, after 2.4 hours and 5 days.
- Sampling intervals/times for pH measurements: For each sampling time the pH value of the solutions was measured.
- Other observation, if any (e.g.: precipitation, colour change etc.): For each sampling time the the visual appearance of the solutions was noted.

Buffers:

Buffer solutions at pH 4.0, 7.0 and 9.0 were prepared. The pH of each buffer solution was checked before use. Each buffer solution was degassed (5 mins, sonicate) to ensure sterility

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: An aliquot of test material (50.041 mg for pH = 4.0, 49.840 mg for pH 7.0 and 50.427 mg for pH= 9.0) was introduced in a volumetric flask (50 mL) and each flask was made to volume with buffer.
- Lighting:The determination was performed in vessels protected from light.
- Stability of test material: The solutions were placed in an oven at approximately +50 °C (temperature was recorded during the test) for up to 5 days.

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

985 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

1 010 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

1 010 mg/L

Number of replicates:

One flask per pH

Positive controls:

no

Negative controls:

no

Preliminary study:

No significant variation of pH was observed for any buffer at any time. At each pH, resulting solutions at the end of the test were colourless. The degradation of the test material at each pH value indicated hydrolysis lower than 10 % after 5 days.

Test performance:

In agreement with the guideline, the test was considered complete after the performance of the preliminary test revealed the test material to be hydrolytically stable.

Transformation products:

no

% Recovery:

104

pH:

4

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

102

pH:

7

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

103

pH:

9

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

4

Temp.:

50 °C

DT50:

> 1 yr

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

7

Temp.:

50 °C

DT50:

> 1 yr

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

9

Temp.:

50 °C

DT50:

> 1 yr

Remarks on result:

hydrolytically stable based on preliminary test

Table 1: Summary of Preliminary Test Results at 50 °C

Sampling Time (hours)	Measured pH	Measured Concentration (mg/L)
		First Assay	Second assay	Mean	Remaining Concentration (%)*
0	3.98	1020	949	985	100
2.4	3.99	1020	1030	1030	105
120	3.96	1020	1010	1020	104
0	7.00	1040	976	1010	100
2.4	6.97	1000	991	996	98.6
120	6.94	1030	1030	1030	102
0	8.94	1020	1000	1010	100
2.4	8.83	1030	1050	1040	103
120	8.34	1050	1030	1040	103

*Calculated using the mean value of T = 0 hour

Validity criteria fulfilled:

yes

Conclusions:

Under the conditions of this study, the test material can be considered as a hydrolytically stable compound and its t1/2 at +25 °C was considered to be greater than 1 year.

Executive summary:

The abiotic degradation (hydrolysis as a function of pH) of the test material was determined in accordance with the standardised guideline EU Method C.7 under GLP conditions.

The abiotic degradation of the test material was estimated in a preliminary test. The determination was undertaken at three pH levels (pH 4.0, 7.0 and 9.0). The test was performed at 50.0 ± 1 °C under sterile conditions and protected from light. The solutions were analysed by High Performance Liquid Chromatography with Ultra-Violet detection at the start of the test and after 2.4 hours and 5 days.

The degradation of the test material, at each pH value, indicated hydrolysis lower than 10 % after 5 days. In agreement with the guideline, the test was considered complete.

Under the conditions of this study, the test material can be considered as a hydrolytically stable compound and its t1/2 at +25 °C was considered to be greater than 1 year.

Description of key information

Under the conditions of this study, the test material can be considered as a hydrolytically stable compound and its t1/2 at +25 °C was considered to be greater than 1 year.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C

Additional information

The abiotic degradation (hydrolysis as a function of pH) of the test material was determined in accordance with the standardised guideline EU Method C.7 under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The abiotic degradation of the test material was estimated in a preliminary test. The determination was undertaken at three pH levels (pH 4.0, 7.0 and 9.0). The test was performed at 50.0 ± 1 °C under sterile conditions and protected from light. The solutions were analysed by High Performance Liquid Chromatography with Ultra-Violet detection at the start of the test and after 2.4 hours and 5 days.

The degradation of the test material, at each pH value, indicated hydrolysis lower than 10 % after 5 days. In agreement with the guideline, the test was considered complete.

Under the conditions of this study, the test material can be considered as a hydrolytically stable compound and its t1/2 at +25 °C was considered to be greater than 1 year.