4H-Pyrido[1,2-a]pyrimidin-4-one, 3-(2-chloroethyl)-9-hydroxy-2-methyl-, hydrochloride (1:1)

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 September - 29 December 2015

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:

3-(2-CHLOROETHYL)-9-HYDROXY-2-METHYL-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ONE HYDROCHLORIDE (1:1)

EC Number:

617-648-0

Cas Number:

849727-62-4

Molecular formula:

C11H11ClN2O2.HCl

IUPAC Name:

3-(2-CHLOROETHYL)-9-HYDROXY-2-METHYL-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ONE HYDROCHLORIDE (1:1)

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Name of test material (as cited in study report): T002006
- Substance type: almost white to ochre solid
- Physical state: solid
- Analytical purity: 97.5%
- Lot/batch No.: I15BB0722
- Expiration date of the lot/batch: 2017-02-21
- Storage condition of test material: At room temperature (15-25°C)

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

1.9

Temp.:

20 °C

pH:

ca. 7

Details on results:

Preliminary test
The content of test item dissolved in the n-octanol sample was 0.384 g/L.

Main study
The analysed concentration of the stock solution was 0.0778 g/L. Based on this, the nominal quantity of the test item in the test samples was 0.156 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 samples from the blank mixture. Detailed results are given in the table in the field 'Any other information on results incl. tables'.

Any other information on results incl. tables

Ratio n-octanol:water (v:v)	Analysed concentration  n-octanol (g/L)  water (g/L)		Pow	Pow (mean)	log Pow		pH
1:1	0.0295	0.000337	8.8E1	8.6E1	1.9		7.1
1:1	0.0286	0.000338	8.4E1		1.9		7.1
1:2	0.0427	0.000496	8.6E1	8.5E1	1.9		7.0
1:2	0.0415	0.000493	8.4E1		1.9		7.0
2:1	0.0235	0.000258	9.1E1	8.5E1	2.0		7.1
2:1	0.0206	0.000264	7.8E1		1.9		7.1
Mean			8.5E1		1.9
Standard deviation			4.5

Recovery was between 106 and 122%.

Applicant's summary and conclusion

Conclusions:

The shake flask method at pH 7 was applied for the determination of the partition coefficient (Pow) of JNJ-1692405-AAC (T002006).

The Pow value of the test item at 20°C was 8.5 x 10^(1). This corresponds to a log Pow value of 1.9.