5-[4-Carboxy-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyrylamino]-2-nitro-benzoic acid, L-

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 August 2015-17 November 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant study in accordance with EC A.8 and OECD 107.

Data source

Reference

Reference 1

Reference Type:

other: study amendment

Title:

Unnamed

Year:

2021

Report date:

2021

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Version / remarks:

(2008)

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:

shake-flask method to: flask method

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

5-[(S)-4-Carboxy-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyrylamino]-2-nitro-benzoic acid

EC Number:

926-197-1

Cas Number:

2561176-48-3

Molecular formula:

C20 H15 N3 O9

IUPAC Name:

5-[(S)-4-Carboxy-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyrylamino]-2-nitro-benzoic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name (as cited in study report): P-Glupa-C
- Appearance: yellow powder
- Storage conditions: at room temperature

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Partition coefficient 1

Type:

Pow

Partition coefficient:

47

Temp.:

20 °C

pH:

1

Remarks on result:

other: Mean value (n=6). Standard deviation: 0.37

Partition coefficient 2

Type:

log Pow

Partition coefficient:

1.7

Temp.:

20 °C

pH:

1

Remarks on result:

other: Mean value (n=6)

Partition coefficient 3

Type:

Pow

Partition coefficient:

< 0.004

Temp.:

20 °C

pH:

7

Remarks on result:

other: highest value

Partition coefficient 4

Type:

log Pow

Partition coefficient:

< -2.4

Temp.:

20 °C

pH:

7

Remarks on result:

other: highest value

Details on results:

SHAKE FLASK AT PH 1
- The analysed concentration of the stock solution was 0.0519 g/L.
- The nominal quantity in each test sample was 0.104 mg.
- The quantity analysed in each test sample ranged from 0.105 to 0.106 mg.
- The recovery ranged from 101% to102%.
- The log Pow values were within the criterion range of ± 0.3 log units.
- No test substance was detected in the pretreated phases from the blank test sample.

SHAKE FLASK AT PH 7
- The analysed concentration of the stock solution was 0.0342 g/L.
- The nominal quantity in each test sample was 0.0685 mg. All recoveries determined with this value approximated 150%. Recoveries calculated with the nominal concentration of te stock solution (i.e. 0.0502 g/L), however, were approximately 100%. The recovery ranged from 100% to 102%. Therefore it was concluded that the concentration of the stock solution was underestimated and results were accepted.
- The quantity analysed in each test sample ranged from 0.101 mg to 0.102 mg.
- The log Pow values were within the criterion range of ± 0.3 log units.
- No test substance was detected in the pretreated phases from the blank test sample.
- As the results were smaller-than values, the highest log Pow and corresponding Pow value rather than the mean is reported. Due to this the standard deviation was not applicable.

Any other information on results incl. tables

Table: Shake-flask at pH 1

  

Ratio n-octanol : water [v:v]	Analysed concentration		Pow		log Pow	pH
	n-octanol [g/L]	water [g/L]	individual	mean
1:1	0.0171	0.000362	4.7E01	4.7E01	1.7	1.0
	0.0172	0.000369	4.7E01		1.7	1.0
1:2	0.0252	0.000540	4.7E01	4.7E01	1.7	1.0
	0.0252	0.000535	4.7E01		1.7	1.0
2:1	0.0131	0.000283	4.6E01	4.6E01	1.7	1.0
	0.0131	0.000280	4.7E01		1.7	1.0

 

Table: Shake-flask at pH 7

 

Ratio n-octanol : water [v:v]	Analysed concentration		Pow		log Pow	pH
	n-octanol [g/L]^1	water [g/L]	individual	mean
1:1	< 0.000048	0.0167	< 2.8E-03	< 2.8 E-03	< -2.5	6.9
	< 0.000048	0.0168	< 2.8E-03		< -2.5	6.9
1:2	< 0.000048	0.0126	< 3.8E-03	< 3.8 E-03	< -2.4	6.9
	< 0.000048	0.0126	< 3.8E-03		< -2.4	6.9
2:1	< 0.000048	0.0252	< 1.9E-03	< 1.9 E-03	< -2.7	6.9
	< 0.000048	0.0255	< 1.9E-03		< -2.7	6.9

¹No response of the test substance was observed in the n-octanol samples. The analysed concentrations were determined using the nominal concentration of the lowest calibration standard, weight of the sample and the dilution factor.

Applicant's summary and conclusion

Conclusions:

Using the shake-flask method in accordance with EC A.8, OECD 107 and EPA OPPTS 830.7550 and in compliance with GLP, the log Pow of P-Glupa-C at 20°C and pH 1 has been determined as 1.7. The log Pow of P-Glupa-C at 20°C and pH 7 has been determined as < -2.4.