Registration Dossier

Administrative data

Endpoint:
partition coefficient
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 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Deviations:
yes
Remarks:
Due to low water solubility and limit of quantification of analytical method, it has been decided in accordance with the sponsor that the partition coefficient was calculated from the single solubilities in both phases and given as appraisal.
GLP compliance:
no
Type of method:
shake-flask method to: flask method
Partition coefficient type:
octanol-water

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)-phenyldiazenyl]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-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)-phenyldiazenyl]pyrimidine-4,6-diamine
Test material form:
solid
Specific details on test material used for the study:
Name: Fluorazopyrimidin
CAS number: 1350653-29-0
Batch-No.: FEY 7260-429-226
Aggregate State at Room Temperature: Solid (powder)
Colour: orange
Purity: 97.6% (CoA)
Date of manufacture: December 19, 2018
Date of CoA: February 08, 2019
Date of recontrol: June 20, 2019
Storage Conditions at Test Facility: At 20 °C ± 5 °C, in the dark

Study design

Analytical method:
high-performance liquid chromatography
mass spectrometry

Results and discussion

Partition coefficient
Key result
Type:
log Pow
Partition coefficient:
> 4.95
Temp.:
20 °C
pH:
6.8
Details on results:
The partition coefficient was calculated based on the results of the analytical determination. The test item content was determined by LC-MS/MS. The difference between the three separate approaches was less than 15 %. Therefore, the study is considered to be valid.
According to this study the logarithmic partition coefficient (n octanol/water) of the test item was determined to be > 4.95 using the shake flask method at 20 ± 0.5°C and pH 6.8.

The water solubility in the study 127251185 could not be determined exactly. A value of < 1.4 µg/L has been given there as appraisal. This value represents the LOQ of the analytical method. Because the real solubility lies below 1.4 µg/L, the partition coefficient will be higher than the calculated value of 4.95.

Applicant's summary and conclusion

Conclusions:
According to this study the logarithmic partition coefficient (n octanol/water) of the test item was determined to be > 4.95 using the shake flask method at 20 ± 0.5°C and pH 6.8.
Executive summary:

Title

Fluorpyrazopyrimidine: Determination of the Partition Coefficient (n-Octanol/Water)

 

Purpose

The purpose of the study was to calculate the partition coefficient of the test item between n-octanol and water using the corresponding solubilities in both phases.

 

Guidelines /Recommendations

This study was based on the procedures indicated by the following internationally accepted methods:

Organization for Economic Co-operation and Development (OECD), OECD Guidelines for Testing of Chemicals, Guideline No.107:”Partition coefficient (n-octanol/water), Shake Flask Method”, adopted July 27, 1995

Commission Regulation (EC) No.440/2008, Annex, Part A, Methods for the determination of physico-chemical properties, A.8”Partition coefficient”, 2008

Product Properties Test Guideline OPPTS 830.7550 of the United States Environment Protection Agency (EPA), August 1996.

 

Results

The partition coefficient was calculated based on the results of the analytical determination. The test item content was determined by LC-MS/MS. The difference between the three separate approaches was less than 15 %. Therefore, the study is considered to be valid.

According to this study the logarithmic partition coefficient (n‑octanol/water) of the test item was determined to be  > 4.95 using the shake flask method at 20 ± 0.5°C and pH 6.8. This study is classified acceptable and satisfies the guideline requirements for partition coefficient studies.