Reaction mass of (S)-2-[(R)-2-Oxo-4-propyl-1-pyrrolidinyl]butyramide and (S)-2-[(S)-2-Oxo-4-propyl-1-pyrrolidinyl]butyramide

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 Jan 2019 - 20 Feb 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - Shake Flask Method)

Version / remarks:

2016

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1995

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1996

Deviations:

no

GLP compliance:

yes

Type of method:

flask method

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (S)-2-[(R)-2-Oxo-4-propyl-1-pyrrolidinyl]butyramide and (S)-2-[(S)-2-Oxo-4-propyl-1-pyrrolidinyl]butyramide

Cas Number:

943986-70-7

Molecular formula:

C11H20N2O2

IUPAC Name:

Reaction mass of (S)-2-[(R)-2-Oxo-4-propyl-1-pyrrolidinyl]butyramide and (S)-2-[(S)-2-Oxo-4-propyl-1-pyrrolidinyl]butyramide

Test material form:

solid

Details on test material:

- Appearance: Off-white solid
- Storage condition of test material: At room temperature protected from light

Study design

Analytical method:

other: UPLC-UV

Results and discussion

Partition coefficient

Partition coefficient 1

Key result

Type:

log Pow

Partition coefficient:

0.9

Temp.:

20 °C

pH:

>= 6.8 - <= 6.9

Remarks on result:

other: non-buffered test system

Partition coefficient 2

Key result

Type:

Pow

Partition coefficient:

7.7

Temp.:

20 °C

pH:

>= 6.8 - <= 6.9

Remarks on result:

other: non-buffered test system

Details on results:

Using the Rekker calculation method the Pow of the test item was calculated to be 4.9 (log Pow 0.69) .

Using the Perrin calculation method the pKa values in the logarithm range of 1 - 14 for acidic and basic groups in the molecular structure of the test item were calculated as follows: no acidic pKa, basic pKa = 1.5 (for RCONH2).

Any other information on results incl. tables

Shake flask method

Analyzed concentrations and Pow of the test item

Ratio n-octanol : water [v:v]	Analyzed concentration		Pow		log Pow	pH
	n-octanol [g/L]	water [g/L]	individual	mean
1:1	0.155	0.0201	7.7	7.8	0.9	6.9
	0.155	0.0195	7.9		0.9	6.9
1:2	0.212	0.0272	7.8	7.7	0.9	6.9
	0.208	0.0274	7.6		0.9	6.9
2:1	0.122	0.0164	7.4	7.4	0.9	6.8
	0.122	0.0164	7.4		0.9	6.8
Mean			7.7		0.9
Standard deviation			1.9x10^-1

The analyzed concentration of the stock solution was 0.591 g/L. Based on this result the nominal quantity of the test item in the test samples was 1.18 mg. The calculated recoveries according to this value ranged from 88 – 90%.

 

Recoveries

Ratio n-octanol : water [v:v]	Used phase volume			Analyzed quantity			Recovery [%]
	stock [mL]	n-octanol [mL]	water [mL]	n-octanol [mg]	water [mg]	total [mg]
1:1	2	4	6	0.928	0.120	1.05	89
				0.928	0.117	1.05	88
1:2	2	2	8	0.847	0.218	1.06	90
				0.833	0.219	1.05	89
2:1	2	6	4	0.974	0.0655	1.04	88
				0.979	0.0657	1.04	88

These recovery values are lower than expected, because the nominal concentration of the stock solution was 0.524 g/L. Based on the nominal stock solution concentration, the expected quantity of the test item in the test samples should be 1.05 mg.When using this value, calculated recoveries would range from 99 – 102%. Considering the good agreement between the expected nominal quantity and the total analyzed quantity of test item in test samples, the partition coefficient results obtained are considered to be accurate.

The log P_ow values were within the criterion range of ± 0.3 log units. The P_ow and log P_ow of the test item is given as the mean value of all measurements.

No test item was detected in the pretreated samples from the blank mixture.

Applicant's summary and conclusion

Conclusions:

The n-octanol - water partition coefficient of the substance at 20°C was determined to be 7.7 (log Pow = 0.9) using the shake flask method (non-buffered test system).