ethyl (2S,3S)-3-aminobicyclo[2.2.2]octane-2-carboxylate monohydrochloride

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 February - 22 March 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

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:

(2S,3S)-3-(ethoxycarbonyl)bicyclo[2.2.2]octan-2-aminium chloride

Cas Number:

1626394-43-1

Molecular formula:

C11H19NO2.HCl

IUPAC Name:

(2S,3S)-3-(ethoxycarbonyl)bicyclo[2.2.2]octan-2-aminium chloride

Test material form:

solid: particulate/powder

Details on test material:

- Physical state: powder
- Appearance: white powder

Specific details on test material used for the study:

- Batch n°: M16HD2757
- Analytical purity: 95.1% (determined by GC assay)
- Expiration date: 04 July 2018
- Storage condition: at room temperature

Study design

Analytical method:

high-performance liquid chromatography

mass spectrometry

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

-0.55

Temp.:

20 °C

pH:

7

Details on results:

Main study: shake flask method
The analysed concentration of the stock solution was 0.948 g/L. Based on this, the nominal quantity of the test item in the test samples was 1.90 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. Detailed results are given in the table in the field 'Any other information on results incl. tables'.
The pH of the blank aqueous samples was 7.1.

Any other information on results incl. tables

Ratio n-octanol:buffer pH 7 (v:v)	Analysed concentration  n-octanol (g/L)  buffer pH 7 (g/L)		Pow	Pow (mean)	log Pow		pH
1:1	0.0774	0.264	2.9 E-1	3.0 E-1	-0.53		7.0
1:1	0.0780	0.248	3.1 E-1		-0.50		7.0
1:2	0.0676	0.214	3.2 E-1	3.1 E-1	-0.50		7.0
1:2	0.0671	0.221	3.0 E-1		-0.52		7.0
2:1	0.0812	0.337	2.4 E-1	2.4 E-1	-0.62		7.0
2:1	0.0798	0.339	2.4 E-1		-0.63		7.0
Mean			2.8 E-1		-0.55
Standard deviation			3.6 E-2

Recovery was between 103 and 108%.

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-63756992-AAC (T003680). At pH 7, the test item is predicted to be in its non-ionised form. The Pow value of the test item at 20°C was 2.8 x 10^(-1). This corresponds to a log Pow value of -0.55.