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Partition coefficient

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Reference
Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 31, 2017- April 11, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method A.8 (Partition Coefficient - Shake Flask Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of method:
flask method
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: yes
Analytical method:
high-performance liquid chromatography
Key result
Type:
log Pow
Partition coefficient:
-3.51
Temp.:
20 °C
pH:
> 3.78 - < 4.09

The test item stock solution was prepared in water pre-saturated with1-octanol.The measuredCytidine 3'-(dihydrogen phosphate) concentration in stock solution (water) was 4.7124 g/kg (4.7124g/L). Density of 1-octanol (supplier data) is 0.825 g/L.

Table 1. Calibration solution

Weight

[mg]

Dilution

[ml]

Cw

[mg/ml]

Peak area

Average

peak area

Aw

f

Average

 f

20.25

25-1-25-2-10

0.0062856

559065

559488

559276.5

0.00001124

0.00001094

25-1-25-3-10

0.0091368

858269

859970

859119.5

0,00001064

25-1-25-0,1-10-2-5-2-10

0.0002344

3716

3656

3686

0.00006610

0.00006918

25-1-25-0,1-10-2-5-2-10

0.0012182

16987

16733

16860

0.00007226

Table 2. Study solution

Sample

 

Weight

of the sample

[mg]

Dilution

[ml]

Cp

[mg/mL]

Peak area

 

Average peak area

Ap

X

[g/kg]

1/w

204.65

25

8.186

725288

726363

725825.5

0.96974

2/w

199.40

25

7.976

702881

703157

703019.0

0.96400

3/w

100.35

25

4.014

254850

258538

256694.0

0.69941

4/w

202.05

25

8.082

509404

509301

509352.5

0.68928

5/w

202.60

25-3-10

2.431

353719

351752

352735.5

1.58694

6/w

202.00

25-3-10

2.424

352469

350838

351653.5

1.58664

stock

93.7

25-4-10

1.4992

645520

646401

645960.5

4.7124

1/o

1636.40

5

327.28

1123

1916

1519.5

0.000321

2/o

2505.30

5

501.06

2634

2667

2650.5

0.000366

3/o

2461.55

5

492.31

2219

2204

2211.5

0.000311

4/o

1802.30

5

360.46

2505

2318

2411.5

0.000463

5/o

2554.30

5

510.86

3518

3200

3359

0.000455

6/o

2502.80

5

500.56

2898

2861

2879.5

0.000398

 

Table 3. Results of measurements at 20.0°C

Vial number

1

2

3

4

5

6

Temperature,°C

20.2

20.1

20.2

Volume of added stock solution, mL

1

1

1

1

1

1

Volume of water, mL

4

4

5.7

5.7

2.3

2.3

Volume of 1-octanol, mL

5

5

3.3

3.3

6.7

6.7

Volume 1-octanol phase/

volume of water phase

1:1

1:2

2:1

Cytidine 3¢-(dihydrogen phosphate)concentration in water phase, g/L

 

0.96974

 

0.96400

 

0.69941

 

0.68928

 

1.58694

 

1.58664

Cytidine 3¢-(dihydrogen phosphate)concentration in 1-octanol phase, g/kg

 

0.00032

 

0.00037

 

0.00031

 

0.00046

 

0.00046

 

0.00040

Cytidine 3¢-(dihydrogen phosphate)concentration in 1-octanol phase, g/L

 

0.00026

 

0.00031

 

0.00026

 

0.00038

 

0.00038

 

0.00033

Mass ofCytidine 3¢-(dihydrogen phosphate)in water phase103, g

4.8487

4.8200

4.6860

4.6182

5.2369

5.2359

Mass of Cytidine 3¢-(dihydrogen phosphate)(5-CMP acid) in 1-octanol phase103, g

0.0013

0.0016

0.0009

0.0013

0.0025

0.0022

Mass ofCytidine 3¢-(dihydrogen phosphate)in both phases103, g

4.8500

4.8216

4.6869

4.6195

5.2394

5.2381

Added mass ofCytidine 3¢-(dihydrogen phosphate)103, g

4.7124

4.7124

4.7124

4.7124

4.7124

4.7124

 

Table 4. Measured pH values of water phase

        Vial number

1

2

3

4

5

6

pH before test

6.09

6.09

6.09

6.09

6.09

6.09

pH after test

 3.99

 4.00

 4.08

 4.09

 3.78

 3.78

 

Table 5. Calculated values of partition coefficient 1-octanol/water 

Vial number

1

2

3

4

5

6

Volume 1-octanol phase/volume of water phase

 

1:1

 

1:2

 

2:1

Pow= C1-octanol/Cwater

0.00027

0.00032

0.00037

0.00055

0.00024

0.00021

log Pow= log(C1-octanol/Cwater)

-3.57

-3.49

-3.43

-3.26

-3.62

-3.68

Average log Pow+ standard deviation

-3.53 ± 0.06

-3.35 ± 0.12

-3.65 ± 0.04

Average log Pow+ standard deviation

-3.51±0.15

 

Conclusions:
The logPow of the test substance at 20 ºC and at pH ranging 3.78-4.09 in water is -3.51 ± 0.15.
Executive summary:

The determination of the partition coefficient 1-octanol/water of the test substance at one pH value was performed according to OECD 107 and EU method A.8 (shake flask method), following GLP. Taking into account the water solubility of the test substance in water and its solubility in 1-octanol, the partition coefficient was calculated. The logPow of the test substance at 20 ºC and at pH ranging 3.78-4.09 in water is -3.51 ± 0.15.

Description of key information

Key study: OECD 107 and EU method A.8. GLP study. The logPow of the test substance at 20 ºC and at pH ranging 3.78-4.09 in water is -3.51 ± 0.15.

Key value for chemical safety assessment

Log Kow (Log Pow):
-3.51
at the temperature of:
20 °C

Additional information

Key study: The determination of the partition coefficient 1-octanol/water of the test substance at one pH value was performed according to OECD 107 and EU method A.8 (shake flask method), following GLP. Taking into account the water solubility of the test substance in water and its solubility in 1-octanol, the partition coefficient was calculated. The logPow of the test substance at 20 ºC and at pH ranging 3.78-4.09 in water is -3.51 ± 0.15.