Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 February 2016 - 06 July 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method A.8 (Partition Coefficient)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of method:
HPLC method
Remarks:
and the Rekker calculation method (preliminary estimation)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study reports): JNJ-17299412-AAA (T001599)
- Physical state: solid (powder)
- Appearance: white powder
Specific details on test material used for the study:
- Batch n°: I15HB2951
- Analytical purity: 100.2% (Based on base titration assay)
- Expiration date: 09 August 2017
- Storage condition: at room temperature

Study design

Analytical method:
high-performance liquid chromatography
photometric method

Results and discussion

Partition coefficientopen allclose all
Key result
Type:
log Pow
Partition coefficient:
3.5
pH:
7
Remarks on result:
other: T not determined
Key result
Type:
log Pow
Partition coefficient:
3.3
pH:
11
Remarks on result:
other: T not determined
Details on results:
Calculation method
Calculation of the Pow: The Pow of the test item was calculated to be 7.2 E+3 (log Pow 3.9) using the Rekker calculation method.
Calculation of the pKa values: basic group (RRNH2+) = pKa 8.6. No pKa values for acidic groups in the molecular structure of the test item in the logarithm range of 1-14 were calculated.

Main study at neutral pH
The equation of the regression line was log k’ = 0.393 x log Pow – 0.802 (r = 0.998, n = 12).

Main study at pH 11
The equation of the regression line was log k’ = 0.386 x log Pow – 0.911 (r = 0.98, n = 12).

Any other information on results incl. tables

Results - neutral pH:

 Substance  tr,1 (min)  tr,2 (min) Mean tr (min)  logPow
 Formamide (t0 )  0.561 0.563  0.562  
 Nitrobenzene  1.032  1.031    1.9
 Bromobenzene  1.978 1.973     3.0
1,4 -Dichlorobenzene 2.628   2.617    3.4
 Biphenyl 3.864  3.834    4.0
1,2,4 -Trichlorobenzene  4.447  4.408    4.2
 Dibenzyl  7.319  7.227    4.8
 Test item  2.595  2.597  2.596  3.5

Results - at pH 11:

 Substance  tr,1 (min)  tr,2 (min) Mean tr (min)  logPow
 Formamide (t0 )  0.542 0.544  0.543  
 Nitrobenzene  0.847  0.850    1.9
Toulene  1.454  1.455    2.7
 Bromobenzene  1.545  1.550    3.0
 1,4 -Dichlorobenzene  1.969  1.977    3.4
 Biphenyl  2.681  2.696   4.0
 1,2,4 -Trichlorobenzene  3.214  3.235    4.2
  Test item  1.752  1.754  1.753  3.3

Applicant's summary and conclusion

Conclusions:
The HPLC method was applied for the determination of the partition coefficient (Pow) of JNJ-17299412-AAA (T001599).

The Pow value of the test item at pH 7 and 11 were found to be 2.9 x 10³ and 1.8 x 10³. These correspond to a log Pow value of 3.5 and 3.3 respectively.