4,6-Pyrimidinediamine, 2-[5-fluoro-1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(1E)-2-phenyldiazenyl]-

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019-04-24 to 2019-06-12

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)

Deviations:

yes

Remarks:

Despite the limited solubility below 10 mg/L, a modified shake flask experiment has been conducted (no time-dependency; no 30°C incubation) in accordance with the sponsor.

GLP compliance:

no

Type of method:

flask method

Test material

Test material information

Constituent 1

Reference substance name:

2-{5-fluoro-1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl}-5-[(1E)-2-phenyldiazen-1-yl]pyrimidine-4,6-diamine

EC Number:

811-933-5

Cas Number:

1350653-29-0

Molecular formula:

C23 H17 F2 N9

IUPAC Name:

2-{5-fluoro-1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl}-5-[(1E)-2-phenyldiazen-1-yl]pyrimidine-4,6-diamine

Test material form:

solid

Results and discussion

Water solubility

Key result

Water solubility:

< 1.4 µg/L

Conc. based on:

test mat.

Loading of aqueous phase:

1 g/L

Incubation duration:

261 h

Temp.:

20 °C

pH:

6.8

Details on results:

Discussion:
As stated in the study plan, the concentrations measured in the vessels should not differ by more than 15% for the test to be seen as satisfactory. This is not the case for the watery samples.
For the determination of very low soluble substances, the column elution method has been designed because the shake flask method resp. similar approaches used for these substances are error-prone, especially during the sampling. Against this background, outlier to higher values has to be eliminated as done in the calculation.
Additionally, the concentration of the test item in water was below limit of quantitation for two of the three evaluated approaches as well as for the average. Therefore the LOQ-value is given here as appraisal.
Result:
The solubility in water of a substance was determined by the saturation mass concentration of the substance in water at a given temperature. The saturation mass concentrations of the test item were determined using LC-MS/MS.
Corresponding to the analyses the water solubility was determined to be <1.4µg/L at 20 ± 0.5 °C. The pH of the saturated solution was 6.8.

Applicant's summary and conclusion

Conclusions:

The solubility in water of a substance was determined by the saturation mass concentration of the substance in water at a given temperature. The saturation mass concentrations of the test item were determined using LC-MS/MS.
Corresponding to the analyses the water solubility was determined to be < 1.4 µg/L at 20 ± 0.5 °C. The pH of the saturated solution was 6.8.

Executive summary:

Title:

Fluorpyrazopyrimidine: Determination of the Water Solubility

 

Purpose:

The purpose of this study was to evaluate the solubility of the test item in water which is specified by the saturation mass concentration of the test item in water at a specified temperature.

 

Guidelines/Recommendations:

This study was based on the procedures indicated by the following internationally recognized documents:

OECD Guidelines for Testing of Chemicals, Guideline No.105, ”Water Solubility”; adopted July 27, 1995

Commission Regulation (EC) No 440/2008, Annex, Part A, Methods for the determination of physico-chemicals properties, A6 "Water Solubility", May 2008

Product Properties Test Guideline of the United States Environment Protection Agency (EPA), OPPTS 830.7840 Water Solubility: Column Elution Method; Shake Flask Method, March 1998

 

Discussion:

As stated in the study plan, the concentrations measured in the vessels should not differ by more than 15% for the test to be seen as satisfactory. This is not the case for the watery samples.

For the determination of very low soluble substances, the column elution method has been designed because the shake flask method resp. similar approaches used for these substances are error-prone, especially during the sampling. Against this background, outlier to higher values has to be eliminated as done in the calculation.

Additionally, the concentration of the test item in water was below limit of quantitation for two of the three evaluated approaches as well as for the average. Therefore the LOQ-value is given here as appraisal.

 

Result:

The solubility in water of a substance was determined by the saturation mass concentration of the substance in water at a given temperature. The saturation mass concentrations of the test item were determined using LC-MS/MS.

Corresponding to the analyses the water solubility was determined to be  < 1.4 µg/L at 20 ± 0.5 °C. The pH of the saturated solution was 6.8.

This study is classified acceptable and satisfies the guideline requirements for water solubility studies.