Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 February 2016 - 11 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

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-17298957-AAA (T001592)
- Physical state: solid (powder)
- Appearance: White powder
Specific details on test material used for the study:
- Batch n°: I15HB2929
- Analytical purity: 100% (Based on base titration assay)
- Expiration date: 14 Aug 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
The Pow of the test item was calculated to be 7.2E+3 (log Pow 3.9) using the Rekker calculation method.
The pKa of the test item owing to its basic group, RRNH2+ was 8.6.

Preliminary test
The amount of test item dissolved in n-octanol was 19.8 g/L.

Main study
-At pH 7:
The retention time of the test item was found to be 2.606 mins and 2.648 minutes.
The equation of the regression line was log k’ = 0.393 × log Pow – 0.802 (r = 0.998, n = 12)
-At pH 11:
The retention times of the test item were 1.750 and 1.754 minutes.
The equation of the regression line was log k’ = 0.386 × log Pow – 0.911 (r = 0.98, n = 12)
In the chromatograms of the test item, at pH 7 and 11, only one test item peak was observed.

Detailed results are given in the table in the field 'Any other information on results incl. tables'.

Any other information on results incl. tables

- Pow of the test and reference items - pH 7

Substance

tr,1 [min]

tr,2 [min]

mean tr (n=2)

Log Pow

Pow

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

2.606

2.648

2.627

3.5

3.0 × 103

- Pow of the test and reference items - pH 11

Substance

tr,1 [min]

tr,2 [min]

mean tr (n=2)

Log Pow

Pow

Formamide (t0)

0.542

0.544

0.543

 

 

Nitrobenzene

0.847

0.850

 

1.9

 

Toluene

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

1.750

1.754

1.752

3.3

1.8 × 103

Applicant's summary and conclusion

Conclusions:
The HPLC method at pH 7 and pH 11 was applied for the determination of the partition coefficient (Pow) of JNJ-17298957-AAA (T001592).

The Pow and log Pow value of the test item at pH 7 were 3.0 × 10³ and 3.5. The Pow and log Pow value of the test item at pH 11 was 1.8 × 10³ and 3.3.