1,6-dichloro-1,6-dideoxy-β-D-fructofuranosyl 4-chloro-4-deoxy-α-D-galactose

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984 - 1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Test item solutions (1 %w/v), buffered at pH 1, 2, 3, 4, 6, 7.5 and 9, were stored for up to 336 days at four of the five study temperatures of 30°, 40°, 50°, 60° and 80°C. Residual test item was analysed by HPLC. The test item sample which underwent maximum breakdown at each pH was further analysed by HPLC to identify and quantify the breakdown products.

GLP compliance:

not specified

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 167002

Analytical monitoring:

yes

Details on sampling:

- Sampling Intervals: Samples were taken at time, t=0, and at four equal intervals during the storage time at each condition. Thus, for example, at pH 1.0 and 30 °C the total storage time was 28 days with samples taken at 0, 7, 14, 21 and 28 days.
- Sample Preparation: Test item solution (1.0 % w/v) were prepared in bulk at each pH, with buffer solutions equilibrated to the appropriate storage temperatures. Control samples were frozen immediately and stored at not more than -10 °C until analysed. For each combination of pH and temperature, 4 replicates were stored at the corresponding temperature. Bulk samples of buffers and buffered solutions of sucralose were stored under the same conditions as the test samples. At each sampling interval, the pH of these solutions was monitored at the temperature of storage.
- Sample Removal: Samples (triplicates) and corresponding buffer blanks were removed from storage at the prescribed times, frozen immediately and maintained at not more than -10°C until analysed.

Buffers:

pH 1.0 250 mL 0.2 M KCl (14.919 g/L)
460 mL 0.2 M HCl
290 mL water

pH 2.0 250 mL 0.2 M KCl
56 mL 0.2 M HCl
694 mL water

pH 3.0 500 mL 0.2 M Potassium citrate (46.044 g/L)
236 mL 0.2 M HCl
264 mL water

pH 4.0 500 mL 0.2 M Potassium citrate
116 mL 0.2 M NaOH (8.0 g/L)
384 mL water

pH 6.0 631.5 mL 0.5 M Na2HPO4 (70.99 g/L)
318.5 mL 0.25 M Citric Acid (52.54 g/L)
50 mL water

pH 7.5 420 mL 0.5M Na2HPO4
80 mL 0.5m NaH2PO4 (78.02 g/L)
500 mL water

pH 9.0 250 mL 0.1M KCl (7.455 g/L)
250 mL 0.1M H3BO3 (6.184 g/L)
113 mL 0.1M NaOH (4.0 g/L)
387 mL water

Details on test conditions:

Circulating water baths were maintained at storage temperatures of 40°C, 50°C, 60°C and 80°C. Samples at 30°C were stored in a constant temperature room with long term stability of +/- 1.0°C.

Number of replicates:

3

Positive controls:

yes

Statistical methods:

First order degradation rate constants at each temperature and pH were determined by the least square exponential fit of the residual concentration of sucralose versus aging period. RS-1 software from BNN Research Systems Inc., Cambridge, mass., USA., was utilised for the statistical analysis to obtain the respective rate constants and their standard deviations.

Transformation products:

yes

No.:

#1

No.:

#2

No.:

#3

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

- Formation and decline of each transformation product during test:
- Pathways for transformation:
-- Products of acid-cataysed breakdown:
--- 4-chloro-4-deoxy-D-galactose
--- 1,6-dichloro-1,6-dideoxy-D-fructose
-- Principal products of alkali-catalysed breakdown:
---3,6-anhydro-1-chloro-1-deoxy-beta-D-fructofuranosyl-4-chloro-4-deoxy-alpha-D-galactopyranoside

% Recovery:

ca. 100

pH:

4.11

Temp.:

30 °C

Duration:

ca. 84 d

% Recovery:

ca. 100

pH:

6.2

Temp.:

30 °C

Duration:

ca. 84 d

% Recovery:

ca. 100

pH:

7.67

Temp.:

30 °C

Duration:

ca. 84 d

% Recovery:

>= 94.17 - <= 94.86

pH:

8.62

Temp.:

30 °C

Duration:

ca. 84 d

Key result

pH:

7.67

Temp.:

30 °C

Hydrolysis rate constant:

ca. 0 d-1

Type:

not specified

Remarks on result:

hydrolytically stable based on preliminary test

Remarks:

no half-time is given, because results show, that sucralose is stable at pH 7.67 and temperature 30 °C

Validity criteria fulfilled:

yes

Conclusions:

The hydrolyses of Sucralose was investigated under different pH-values and at different temperature conditions. At pH 4.11; 6.2 and 7.67 the recovery of sucralose was 100 % after 84 days at 30 °C storage conditions. For pH 8.62 the recovery of Sucralose was ca. 94% after 84 days at 30 °C storage conditions.

Description of key information

Hydrolyses of Sucralose was investigated under different pH-values and at different temperature conditions in an well documented test according to scientific principles. At pH 4.11, 6.2 and 7.67 the recovery of sucralose was 100 % after 84 days at 30°C storage conditions. For pH 8.62 the recovery of Sucralose was ca. 94% after 84 days at 30°C storage conditions.

Additional information

No hydrolysis could be observed at neutral pH after 84 days at 30°C.