Cytidine 3'-(dihydrogen phosphate)

Partition coefficient

Link to relevant study record(s)

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 phase∙10^3, 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 phase∙10^3, g	0.0013	0.0016	0.0009	0.0013	0.0025	0.0022
Mass ofCytidine 3^¢-(dihydrogen phosphate)in both phases∙10^3, g	4.8500	4.8216	4.6869	4.6195	5.2394	5.2381
Added mass ofCytidine 3^¢-(dihydrogen phosphate)∙10^3, 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.