4-[(2E)-3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl]-N-[(4R)-2-ethyl-3-oxo-1,2-oxazolidin-4-yl]-2-methylbenzamide

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

1995

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

column elution method

Test material

Test material information

Constituent 1

Reference substance name:

4-[3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl]-N-(2-ethyl-3-oxo-1,2-oxazolidin-4-yl)-2-methylbenzamide

Molecular formula:

C23H18Cl2F4N2O4

IUPAC Name:

4-[3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl]-N-(2-ethyl-3-oxo-1,2-oxazolidin-4-yl)-2-methylbenzamide

Test material form:

solid

Details on test material:

Off-white

Results and discussion

Water solubility

Key result

Water solubility:

0.1 mg/L

Conc. based on:

test mat.

Temp.:

20 °C

pH:

>= 5.82 - <= 5.98

Applicant's summary and conclusion

Conclusions:

The substance has a water solubility of 0.1 mg/L at 20 °C.

Executive summary:

The water solubility of the substance was determined under GLP to OECD TG 105, using the column elution method. The approximate solubility of the substance was estimated visually in a preliminary study and found to be less than 7 mg/L. Therefore, the column elution method was selected to determine the water solubility in the main experiment.

The apparatus used in this column elution study consisted of a microcolumn maintained at the test temperature of 20 °C. It was connected to a levelling vessel. The column contain glass beads, held in place by a small plug of glass wool, which also served to filter out particles. The microcolumn had a headspace providing five bed volumes and was fitted with a one-way stopcock. The flow rate from the levelling vessel was initially set to 25 mL/hour.

In the experiment at a flow rate of 25 mL/h the collection time for each sample was thirty minutes. Successive eluate fractions were collected and analyzed using an appropriate reversed phase HPLC method demonstrating acceptable recovery, linearity and specificity, thus showing that precision and accuracy of the method had been established. These samples were visually checked for the presence of colloidal particles and the pH of each these samples was determined using a pH meter.

After the experiment using a flow rate of 25 mL/h was complete a second run was performed at 12.5 mL/h. The results of the two runs were in good agreement.

In the experiment at a flow rate of 12.5 mL/h the collection time for each sample was one hour. A comparison of the retention times of the test substance in the reference solutions with those in the sample solutions indicated that the identity of the test item had not altered during the experiment.

The results shown are for the final six fractions of the columns from both the flow rates, in which the concentration of the test substance were constant within ± 30%. The six determinations at the higher flow rate of 25 mL/h (pH ranging from 5.82 to 5.95) resulted in solubilities of 85.7 to 99.7 μg/L at 20 °C, with an average of 92.9 μg/L and a relative standard deviation of 6.0%. The six determinations at the flow rate of 12.5 mL/h (pH ranging from 5.83 to 5.98) resulted in solubilities of 108.3 to 114.8 μg/L at 20 °C, with an average of 113.5 μg/L and a relative standard deviation of 4.8%.

The final, average solubility was 100 μg/L at 20 °C, with a relative standard deviation of 11.5%. No colloidal particles were observed in either experiment.