Benzoyl chloride, 4-[[(2-methoxybenzoyl)amino]sulfonyl]-

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 Apr 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

no

Radiolabelling:

no

Analytical monitoring:

yes

Remarks:

HPLC-UV

Details on sampling:

- Sampling method: Aliquots of the dilutions were taken and tempered at 50°C for 2.5 hours.

Buffers:

- pH: 4, 7 and 9

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks: volumetric flasks
- other equipment used: ultrasonic bath

TEST MEDIUM
- Volume used: 25 mL
- Kind and purity of water: distilled water

Duration:

2.5 h

pH:

4

Temp.:

50 °C

Remarks:

Preliminary test

Duration:

2.5 h

pH:

7

Temp.:

50 °C

Remarks:

Preliminary test

Duration:

2.5 h

pH:

9

Temp.:

50 °C

Remarks:

Preliminary test

Number of replicates:

1 replicate for each pH value and temperature.

Positive controls:

not specified

Negative controls:

not specified

Preliminary study:

The experiments using buffers at pH 4, pH 7 and pH 9 as well as the experiment with distilled water showed that the test substance is not stable in contact with water.

Test performance:

The degradation was so fast, that the test substance could not be detected by HPLC and LC-MS.

Transformation products:

yes

No.:

#1

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

- Formation and decline of each transformation product during test: A by-product could be detected in all experiments (approx. 7 % at pH 9) through the area percentage ratio between the peaks.
- Pathways for transformation: HPLC analyses indicated that the hydrolysis yields the corresponding carbonic acid as the main component.

Remarks on result:

not determinable

Remarks:

The degradation was so fast, that the test substance could not be detected by HPLC and LC-MS. The period of time between starting the hydrolysis (contact with water) and injection into the HPLC-system was max. 30 min. Therefore the resulting half-life time was estimated to be below 10 min.

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes
- Anomalies or problems encountered: The degradation was so fast, that the test substance could not be detected by HPLC and LC-MS. The period of time between starting the hydrolysis (contact with water) and injection into the HPLC-system was max. 30 min. Therefore the resulting half-life time was estimated to be below 10 min.

MAJOR TRANSFORMATION PRODUCTS
A by-product could be detected in all experiments (approx. 7 % at pH 9). HPLC analyses indicated that the hydrolysis yields the corresponding carbonic acid as the main component.

PATHWAYS OF HYDROLYSIS
- Description of pathways: HPLC analyses indicated that the hydrolysis yields the corresponding carbonic acid as the main component.
- Figures of chemical structures attached: Yes

SUPPLEMENTARY EXPERIMENT:
In order to verify that the test substance was present before conducting the hydrolysis experiments, the substance was converted with cyclo-propylamine by derivatization. The derivatization experiment approved that the derivatized substance was present, yielding 93 % of the theoretical amount, considering the purity of the test substance (92.6 %).

Validity criteria

Target condition according to guideline:	Actual condition according to the study:	Validity criteria met:
The analytical method 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. However the substance was unstable and undetected.	Yes
The method must be specific to allow determination of the test substance at the test solution concentrations and may well consist of some combination of suitable analytical techniques.	The derivatized product of the test substance could be measured by the analytical method	Yes
The test substance should be dissolved in the selected buffer and the concentration should not exceed 0.01 M or half the saturation concentration, whichever is the lower.	57 mg (pH 7) were dissolved in 25 mL (i.e. 4.4E-3 mol/L)	Yes

Validity criteria fulfilled:

yes

Remarks:

See more details in the table in the section "Any other information on results incl. tables"

Conclusions:

The test substance is not stable in contact with water.

Executive summary:

Hydrolysis of the test substance at 53.9 mg (pH 4), 56.9 mg (pH 7) and 58.3 mg (pH 9) dissolved in buffer of volume of 25 mL was studied for 2.5 h. The experimental protocol is comparable to preliminary test of the EU method C.7 (Degradation: Hydrolysis as a function of pH). Aliquots of the dilutions were taken and tempered at 50°C for 2.5 hours. The solutions were analysed by HPLC before and after the tempering period. Identification of the transformation products was done by HPLC and LC-MS.
The experiments using buffers at pH 4, pH 7 and pH 9 showed that the test substance is not stable in contact with water. The degradation was so fast, that the test substance could not be detected by HPLC and LC-MS. The period of time between starting the hydrolysis (contact with water) and injection into the HPLC-system was max. 30 min. Therefore the resulting half-life time was estimated to be below 10 min. A by-product could be detected in all experiments (approx. 7 % at pH 9). HPLC analyses indicated that the hydrolysis yields the corresponding carbonic acid as the main component and this was confirmed using LC/MS analyses.
In order to verify that the test substance was present before conducting the hydrolysis experiments, the substance was converted with cyclo-propylamine by derivatization. The derivatization experiment approved that the derivatized substance was present, yielding 93 % of the theoretical amount.

Description of key information

Hydrolysis of the test substance at 53.9 mg (pH 4), 56.9 mg (pH 7) and 58.3 mg (pH 9) dissolved in buffer of volume of 25 mL was studied for 2.5 h. The experimental protocol is comparable to preliminary test of the EU method C.7 (Degradation: Hydrolysis as a function of pH). Aliquots of the dilutions were taken and tempered at 50°C for 2.5 hours. The solutions were analysed by HPLC before and after the tempering period. Identification of the transformation products was done by HPLC and LC-MS.
The experiments using buffers at pH 4, pH 7 and pH 9 showed that the test substance is not stable in contact with water. The degradation was so fast, that the test substance could not be detected by HPLC and LC-MS. The period of time between starting the hydrolysis (contact with water) and injection into the HPLC-system was max. 30 min. Therefore the resulting half-life time was estimated to be below 10 min. A by-product could be detected in all experiments (approx. 7 % at pH 9). HPLC analyses indicated that the hydrolysis yields the corresponding carbonic acid as the main component and this was confirmed using LC/MS analyses.
In order to verify that the test substance was present before conducting the hydrolysis experiments, the substance was converted with cyclo-propylamine by derivatization. The derivatization experiment approved that the derivatized substance was present, yielding 93 % of the theoretical amount.