3-[(phenylcarbamoyl)amino]phenyl 4-methylbenzenesulfonate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 June 2018 - 19 June 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

13 April 2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Storage conditions: The test material was stored in a dark storage place at room temperature.

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- The concentration of the test material in the LC-MS analytical sample was calculated proportionally by comparing the peak area of the LC-MS analytical sample with that of 5.05 μg/L standard solution.

Buffers:

- pH 4.0: The solution was prepared by mixing 4.5 mL of 1 mol/L sodium hydroxide solution and 50 mL of 0.5 mol/L potassium dihydrogen citrate solution, and then filling up to 500 mL with purified water, and then adjusting to pH 4.0 with 1 mol/L hydrochloric acid.

- pH 7.0: The solution was prepared by mixing 14.8 mL of 1 mol/L sodium hydroxide solution and 50 mL of 0.5 mol/L potassium dihydrogenphosphate solution, filling up to 500 mL with purified water.

- pH 9.0: The solution was prepared by mixing 10.7 mL of 1 mol/L sodium hydroxide solution and 50 mL of 0.5 mol/L potassium chloride and 0.5 mol/L boric acid solution, filling up to 500 mL with purified water, and then adjusting to pH 9.0 with 1 mol/L sodium hydroxide solution.

Details on test conditions:

TEST SYSTEM
- Dry thermobath: MG-1 (Tokyo Rikakikai Co. Ltd.)
- Test vessel: 10 mL test tube with ground stopper (test vessels were covered with aluminium foil).

TEST CONDITIONS
- Measurement point: At initiation and after 5 days (at each pH).
- Light condition: Light free conditions

PREPARATION OF TEST MATERIAL SOLUTION
- The test sample (10.35 mg, corresponding to 10.11 mg of the test material) was precisely weighed and put into a 20 mL volumetric flask, and then dissolved and filled up in acetonitrile to obtain 505 mg/L solution of the test material.
- An aliquot (1 mL) of the solution of the test material was pipetted into a 10 mL volumetric flask and filled up with acetonitrile to prepare a 50.5 mg/L solution of the test material.
- An aliquot (1 mL) of the solution of the test material was pipetted into a 50 mL volumetric flask and filled up with acetonitrile to prepare a 1.01 mg/L solution of the test material.

PREPARATION FOR STANDARD SOLUTION AND CALCULATION OF CONCENTRATION
- The test material solution (505 mg/L) was then diluted with acetonitrile/purified water (1/1 v/v) to prepare a 5.05 μg/L standard solution.

CALCULATION FOR RESIDUAL PERCENTAGE OF TEST MATERIAL
- The residual percentage of the test material was calculated using the following equation:

Residual percentage of test material (%) = (C/Ci) x 100

Where:
Ci: Concentration of test material at initiation (μg/L)
C: Concentration of test material after 5 days (μg/L)

The test material was judged to be hydrolytically stable in case that the residual percentage of the test material was > 90 %.

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

9.21 µg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

8.55 µg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

7.51 µg/L

Number of replicates:

1 analysis at initiation, duplicate analyses at 5 days.

Positive controls:

not specified

Negative controls:

not specified

Test performance:

At pH 4.0 the concentration at initiation was 9.21 μg/L, after 5 days this was 8.80 and 9.67 per replicate. The average residual percentage after 5 days was 100 %.

At pH 7.0 the concentration at initiation was 8.55 μg/L, after 5 days this was 8.54 and 8.82 per replicate. The average residual percentage after 5 days was 101 %.

At pH 9.0 the concentration at initiation was 7.51 μg/L, after 5 days this was 7.56 and 7.13 per replicate. The average residual percentage after 5 days was 97.9 %.

As the results of residual percentage of the test material were larger than 90 %, the test material was considered to be hydrolytically stable at pH 4.0, 7.0 and 9.0.

Transformation products:

not measured

% Recovery:

100

pH:

4

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

101

pH:

7

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

97.9

pH:

9

Temp.:

50 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

pH:

4

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

pH:

7

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

pH:

9

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

 Summary of results

Test solution	Concentration (μg/L		Residual percentage after 5 days (%)
	At initiation	After 5 days	Measured Value	Average
pH 4.0	9.21	8.80 9.67	95.5 105	100
pH 7.0	8.55	8.54 8.82	99.8 103	101
pH 9.0	7.51	7.56 7.13	101 94.9	97.9

Validity criteria fulfilled:

yes

Conclusions:

Under the conditions of the study the test material is hydrolytically stable at pH 4.0, 7.0 and 9.0.

Executive summary:

The hydrolytic properties of the test material were assessed using a HPLC method, in accordance with the standardised guidelines OECD 111, under GLP conditions. 

The preliminary test (Tier 1) was performed using three buffer solutions at pH 4.0, 7.0 and 9.0. The test material concentrations after 5 days were measured by LC-MS. The test material concentration was determined by the absolute calibration curve method using one concentration of the standard solution, after which the residual percentage of the test material was calculated. As a result, the residual percentage of the test material was larger than 90 %, therefore, under the conditions of the study the test material is hydrolytically stable at pH 4.0, 7.0 and 9.0. 

Description of key information

The test material is hydrolytically stable at pH 4.0, 7.0 and 9.0. 

Additional information

The hydrolytic properties of the test material were assessed using a HPLC method, in accordance with the standardised guidelines OECD 111, 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 preliminary test (Tier 1) was performed using three buffer solutions at pH 4.0, 7.0 and 9.0. The test material concentrations after 5 days were measured by LC-MS. The test material concentration was determined by the absolute calibration curve method using one concentration of the standard solution, after which the residual percentage of the test material was calculated. As a result, the residual percentage of the test material was larger than 90 %, therefore, under the conditions of the study the test material is hydrolytically stable at pH 4.0, 7.0 and 9.0.