Pyrrolidinium, 1-[[(6R,7R)-7-amino-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-methyl-, chloride

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Only the preliminary test at 50 °C was performed.

Reason / purpose for cross-reference:

other: Analytical method.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

2004

Deviations:

yes

Remarks:

Only the preliminary test at 50 °C was performed.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

yes

Remarks:

Only the preliminary test at 50 °C was performed.

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

pH 4.0: 1 mL 0.2 M Sodium hydroxide and 125 mL 0.2 M Potassium hydrogen phthalate were diluted to 500 mL with ultra-pure water
pH 7.0: 74 mL 0.2 M Sodium hydroxide and 125 mL 0.2 M Potassium dihydrogen phosphate were diluted to 500 mL with ultra-pure water
pH 9.0: 53.5 mL 0.2 M Sodium hydroxide and 125 mL 0.2 M Boric acid and Potassium chloride were diluted to 500 mL with ultra-pure water.
The test item concentrations in the buffer solutions were: ~600 mg/L ≈ 1.8-1.9 mM/L.

Details on test conditions:

The hydrolysis was examined at three different pH values 4, 7 and 9 in the dark.
Temperature: 50 °C ± 0.5 °C.
Light and oxygen: The hydrolysis reaction was carried out using a dark thermostat to avoid photolytic effects. Nitrogen was bubbled into the water for five minutes before the preparation of the solutions in order to exclude oxygen.
All glassware, water and buffer solution were sterilised.
From each buffer solution 3 samples of ~25 mL were stored at a temperature of 50 °C in screw-cap glass tubes with PTFE septa.
Additionally, control buffer samples were stored at the same temperature.
Concentration of the test item was determined at the start and at the end of incubation period (after 5 days).
The pH of each buffer solution was checked with a calibrated pH meter at the start and at the end of the test.

Preliminary study:

At pH 4 the concentration of the test item was decreased by about 98.5 %, at pH 7 by 91.9 % and at pH 9 the concentration of the test item was decreased by about 99.5 % after 5 days at 50°C.

Transformation products:

not measured

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

At pH 4 the concentration of the test item was decreased by about 98.5 %, at pH 7 by 91.9 % and at pH 9 the concentration of the test item was decreased by about 99.5 % after 5 days at 50°C.

Key result

pH:

4

Temp.:

50 °C

DT50:

< 5 d

Type:

not specified

Key result

pH:

7

Temp.:

50 °C

DT50:

< 5 d

Type:

not specified

Key result

pH:

9

Temp.:

50 °C

DT50:

< 5 d

Type:

not specified

Details on results:

At pH 4 the concentration of the test item was decreased by about 98.5 %, at pH 7 by 91.9 % and at pH 9 the concentration of the test item was decreased by about 99.5 % after 5 days at 50°C.

Conclusions:

At pH 4 the concentration of the test item was decreased by about 98.5 %, at pH 7 by 91.9 % and at pH 9 the concentration of the test item was decreased by about 99.5 % after 5 days at 50°C.

Executive summary:

Hydrolysis of the test item in different pH buffer solutions was determined at 50 °C ± 0.5 °C.

At pH 4 the concentration of the test item was decreased by about 98.5 %, at pH 7 by 91.9 % and at pH 9 the concentration of the test item was decreased by about 99.5 % after 5 days at 50°C.

Based on the results obtained, the test item can be considered as hydrolytically unstable at pH 4, pH 7 and pH 9 under the conditions investigated.

Description of key information

Hydrolysis of the test item in different pH buffer solutions was determined after 5 days at storage of 50 °C. The decrease of the concentration of the test substance was:

98.5 % at pH 4,

91.9 % at pH 7, and

99.5 % at pH 9.

Based on the results obtained, the test item can be considered as hydrolytically unstable at pH 4, pH 7 and pH 9 under the conditions. The estimated half-life at pH7 is ca. 1.4 d at 50 °C.

Key value for chemical safety assessment

Half-life for hydrolysis:

1.4 d

at the temperature of:

50 °C