N-phenyl-N-piperidin-4-ylpropionamide

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 November 2015 - 24 May 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7550 (Partition Coefficient, n-octanol / H2O, Shake Flask Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

N-phenyl-N-piperidin-4-ylpropionamide

EC Number:

216-543-3

EC Name:

N-phenyl-N-piperidin-4-ylpropionamide

Cas Number:

1609-66-1

Molecular formula:

C14H20N2O

IUPAC Name:

N-phenyl-N-piperidin-4-ylpropionamide

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study reports): JNJ-1594255-AAA (T000425)
- Physical state: solid (powder)
- Appearance: white

Specific details on test material used for the study:

- Batch n°: I15KB4578 (main test) and I13DB1857 (preliminary test)
- Analytical purity: 99.3% (I15KB4578, base titration) and 99.4% (I13DB1857, base titration)
- Expiration date: 26 November 2017 (I15KB4578) and 24 November 2015 (I13DB1857)
- Storage condition: at room temperature

Study design

Analytical method:

high-performance liquid chromatography

photometric method

Results and discussion

Partition coefficient

Partition coefficient 1

Type:

log Pow

Partition coefficient:

-1.5

Temp.:

20 °C

pH:

7.1

Partition coefficient 2

Type:

log Pow

Partition coefficient:

1.3

Temp.:

20 °C

pH:

12.7

Details on results:

Preliminary test:
The content of test item dissolved in the n-octanol sample was 483 g/L.

Shake flask method at pH 7:
The analysed concentration of the stock solution was 0.260 g/L. Based on this, the nominal quantity of the test item in the test samples was 0.520 mg. The recoveries were determined according to this value. The log Pow values were within the criterion range of ± 0.3 log units. Based on this, the Pow and log Pow of the test item is given as the mean value of all measurements. No test item was detected in the pre-treated sample from the blank mixture. Detailed results are given in the table in the field 'Any other information on results incl. tables'.

Shake flask method at pH 13:
The analysed concentration of the stock solution was 0.158 g/L. Based on this the nominal quantity of the test item in the test samples was 0.316 mg. The recoveries were determined according to this value. The log Pow values were within the criterion range of ± 0.3 log units. Based on this, the Pow and log Pow of the test item is given as the mean value of all measurements. No test item was detected in the pre-treated sample from the blank mixture.

Any other information on results incl. tables

Results of the shake flask method at pH 7:

Ratio n-octanol:water (v:v)	Analysed concentration  n-octanol (g/L)  water (g/L)		Pow	Pow (mean)	log Pow		pH
1:1	0.00258	0.0811	3.2E-2	3.2E-2	-1.5		7.1
1:1	0.00260	0.0816	3.2E-2		-1.5		7.1
1:2	0.00198	0.0627	3.2E-2	3.1E-2	-1.5		7.1
1:2	0.00201	0.0642	3.1E-2		-1.5		7.1
2:1	0.00377	0.120	3.1E-2	3.1E-2	-1.5		7.1
2:1	0.00388	0.124	3.1E-2		-1.5		7.1
Mean			3.2E-2		-1.5
Standard deviation			2.4E-4

Recoveries were between 97 and 101% at pH 7.

Results of shake flask method at pH 13:

Ratio n-octanol:water (v:v)	Analysed concentration  n-octanol (g/L)  water (g/L)		Pow	Pow (mean)	log Pow		pH
1:1	0.0512	0.00233	2.2E+1	2.2E+1	1.3		12.7
1:1	0.0510	0.00227	2.2E+1		1.4		12.7
1:2	0.0742	0.00329	2.3E+1	2.2E+1	1.4		12.7
1:2	0.0728	0.00332	2.2E+1		1.3		12.7
2:1	0.0381	0.00184	2.1E+1	2.1E+1	1.3		12.7
2:1	0.0386	0.00183	2.1E+1		1.3		12.7
Mean			2.2E+1		1.3
Standard deviation			7.4E-1

Recoveries were between 97 and 102% at pH 13.

Applicant's summary and conclusion

Conclusions:

The shake flask method at pH 7 and pH 13 was applied for the determination of the partition coefficient (Pow) of JNJ-1594255-AAA (T000425).

The Pow value of the test item at 20°C was 3.2E-2 at pH 7 and 2.2E1 at pH 13. This corresponds to a log Pow value of -1.5 at pH 7 and 1.3 at pH 13.