Reaction mass of 2-(3-{6-[3-(2-Hydroxyethyl)-3-methylureido]hexyl}-1-methylureido)ethanol and 6-[3-(2-Hydroxyethyl)-3-methylureido]hexylamino 3-(methylamino)propionate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

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)

Deviations:

no

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:

Samples were taken at time 0h, 2h, 19h 24h, 90h and 120h (rounded values).

Buffers:

Buffer pH 4 Citric acid/NaOH/NaCl; Fluka, order no.: 33643
Buffer pH 7 KH2PO4/Na2HPO4, Fluka, order no.: 33646
Buffer pH 9 Na2B4O7/HCl, Fluka, order no.: 33648

Details on test conditions:

The substance was dissolved in buffer solution leading to a test item concentration of about 100 mg/L.
Aliquots of the stock solution were taken to obtain individual vials for every test point. To avoid the presence of oxygen the preparation was carried out under nitrogen as flushing gas,.
The vials were closed and incubated at 50 °C in a water bath under dark conditions to avoid any photolytic effects.
At each test point the hydrolysis solution was directly led to the chromatographic measurement.
The pH of the blank buffer solution was checked at the beginning of the test. Additionally the pH of the hydrolysis solution was measured at each test point.
The suitability of the HPLC system during the hydrolysis study was verified on every day of application. The calibration was verified daily at the level of 108 mg/L by using a control calibration solution.

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

100 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

100 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

100 mg/L

Preliminary study:

The overall degradation of the test item at 50 °C at pH 4, 7 and 9 after 5 days is less than 10 %. Therefore no main test was performed.

Transformation products:

no

pH:

4

Temp.:

50 °C

DT50:

> 5 d

Type:

not specified

Remarks on result:

hydrolytically stable based on preliminary test

pH:

7

Temp.:

50 °C

DT50:

> 5 d

Type:

not specified

Remarks on result:

hydrolytically stable based on preliminary test

pH:

9

Temp.:

50 °C

DT50:

> 5 d

Type:

not specified

Remarks on result:

hydrolytically stable based on preliminary test

Details on results:

The overall degradation of the test item at 50 °C at pH 4, 7 and 9 after 5 days is less than 10 %. The test item is therefore considered to be stable at 50 °C at pH 4 and no half-life time and hydrolysis rate were calculated. Because no degradation was observed, no sterility test was performed in this case. No further tests at other temperatures are required

Validity criteria fulfilled:

yes

Conclusions:

The substance is hydrolytically stable at 50 °C at pH 4, 7 and 9.

Executive summary:

In a test according to OECD 111, the overall degradation of the test item at 50 °C at pH 4, 7 andafter 5 days is less than 10 %. The substance is therefore considered to be stable at 50 °C at pH 7 and no half-life time and hydrolysis rate were calculated. Because no degradation was observed, no sterility test was performed in this case. No further tests at other temperatures are required.

Description of key information

The overall degradation of the test item at 50 °C at pH 4, 7 and 9 after 5 days is less than 10 %. The substance is therefore considered to be stable at 50 °C at pH 7 and no half-life time and hydrolysis rate were calculated.