(2S)-[[(benzyloxy)carbonyl]amino](cyclohexyl)acetic acid

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-01-12 to 2007-02-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study performed according to OECD Guideline 111 (Hydrolysis as a Function of pH) and EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH) without deviations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

Remarks:

The testing facility indicated that the protocol was followed without deviation.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Remarks:

The testing facility indicated that the protocol was followed without deviation.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): VRT-126016
- Molecular formula (if other than submission substance): not applicable
- Molecular weight (if other than submission substance): not applicable
- Smiles notation (if other than submission substance): not applicable
- InChl (if other than submission substance): not applicable
- Structural formula attached as image file (if other than submission substance): not applicable
- Substance type: no data
- Physical state: white to off-white powder
- Analytical purity: 99.8 area% by High Performance Liquid Chromatography (HPLC)
- Impurities: chloride: <0.1%
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: 2006-02-02
- Lot/batch No.: 25719
- Expiration date of the lot/batch: February 2008
- Stability under test conditions: no data
- Storage condition of test material: at room temperature
- Other: no data

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
Not applicable

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: 5 minutes, 2.4 h, 120 h
- Sampling method: Duplicate 1 mL aliquots of test solution were added to separate 100mL Wheaton vials containing each buffer solution (100mL), which had been purged with nitrogen and equilibrated to test temperature. Samples were placed in the waterbath at 50 deg C in the dark until sampling was required. At each sampling time, an aliquot was diluted to 10 mL with mobile phase for HPLC analysis.
- Sampling methods for the volatile compounds, if any: not applicable
- Sampling intervals/times for pH measurements: not applicable
- Sampling intervals/times for sterility check: not applicable
- Sample storage conditions before analysis: not applicable
- Other observation, if any (e.g.: precipitation, color change etc.): not applicable

Buffers:

- pH: 4.0
- Type and final molarity of buffer: Potassium dihydrogen orthophosphate; molarity not provided
- Composition of buffer: Potassium dihydrogen orthophosphate (6g), and disodium orthophosphate dodecahydrate (12.8 g), in 1900 mL puified water, pH adjusted to 4.0 +/- 0.05 with orthophosphoric acid, and brought to 2 L with purified water.

- pH: 7.0
- Type and final molarity of buffer: Potassium dihydrogen orthophosphate; molarity not provided
- Composition of buffer: Potassium dihydrogen orthophosphate (27 g) in 3800 mL purified water, 120 mL 1M sodium hydroxide, pH adjusted to 7.0 +/- 0.05 with 1M HCl. Brought to 4L with purified water.

- pH: 9.0
- Type and final molarity of buffer: Disodium tetraborate decahydrate; molarity not provided
- Composition of buffer: Disodium tetraborate decahydrate (66.4 g), Potassium dihydrogen orthophosphate (7.2 g) in 3800 mL purified water, pH adjusted to 9.0 +/- 0.05 with 1M HCl. Brought to 4L with purified water.

Estimation method (if used):

not applicable

Duration of test

Duration of test 1

Duration:

120 h

pH:

4

Initial conc. measured:

101 mg/L

Duration of test 2

Duration:

120 h

pH:

7

Initial conc. measured:

103 mg/L

Duration of test 3

Duration:

120 h

pH:

9

Initial conc. measured:

105 mg/L

Number of replicates:

The test was run in duplicate.

Positive controls:

no

Negative controls:

no

Statistical methods:

Not applicable

Results and discussion

Preliminary study:

Results from the preliminary investigation showed that there was no significant change in the concentration of the test substance when incubated in pH 4, 7 and 9 buffer solution at 50 +/- 0.5 deg C. Less than 10% hydrolysis had occurred after 120 hours (5 days) under these conditions, equivalent to a half-life of greater than 1 year under environmental conditions (25 deg C).

Test performance:

No further testing was required beyond the preliminary study.

Transformation products:

no

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

- Formation and decline of each transformation product during test: not applicable
- Pathways for transformation: not applicable
- Other: not applicable

Other kinetic parameters:

Not applicable

Details on results:

Not applicable

Any other information on results incl. tables

This preliminary study showed that at pH 4, 7, and 9, and at 50 deg C, less than 10% hydrolysis occurred after 120 hours, equivalent to a half life of greater than 1 year under environmental conditions. The test substance was determined to be hydrolytically stable under acidic, neutral and basic conditions. Per the method, no addition testing is required.

Applicant's summary and conclusion

Conclusions:

The test substance was determined to be hydrolytically stable under acidic, neutral, and basic conditions.

Executive summary:

Not applicable