(2S)-2-amino-3-(4-{[bis(sodiooxy)phosphoryl]oxy}phenyl)propanoic acid

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2020-02-24 to 2020-07-15

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:

estimation method (solubility ratio)

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Type:

Pow

Partition coefficient:

< 0

Temp.:

20 °C

pH:

>= 7.1 - <= 7.2

Key result

Type:

log Pow

Partition coefficient:

< -4.59

Temp.:

20 °C

pH:

>= 7.1 - <= 7.2

Preliminary Tests

According to the preliminary test at room temperature, the 1-octanol solubility of the test item was estimated to be < 0.2201 g/L.

Table 2: Preliminary test for the 1-octanol solubility

Amount of test item [mg]	Total volume of added 1-octanol [mL]	Stirring time at RT [min]	Remark
190	5	45	not dissolved
	35	45	not dissolved
30.82	10	970	not dissolved
	40	55	not dissolved
	90	50	not dissolved
	140	340	not dissolved

With the estimated range of the water solubility of the test item estimated in a preliminary test (1061 -2318 g/L) and the estimated solubility in 1-octanol from this preliminary test, the partition coefficient can be estimated to be <2.

Due to this result, the partition coefficient in this study is calculated from the solubilities of the test item in the pure solvents water and 1-octanol. The solubility in 1-octanol is determined by the flask method analogous to EC A.6., OECD 105.

Main Test (flask method)

For the main test three flasks were prepared with an amount of test item and 1-octanol (1a, 2a and 3a), and one flask only with 1-octanol (4a, blank). After stirring and centrifugation the 1-octanol phases were measured by means of HPLC. The solution of each flask has been measured twice.

Table 3: Results of the flask method

Flask	1a	2a	3a	4a
measured value [mg/L]	<13.22	<13.22	<13.22	0.00 / 0.00
average 1-octanol solubility [mg/L]	<13.22	<13.22	<13.22	0.00
mean value of the 1-octanol solubility [mg/L]	<13.22			0.00
standard deviation [mg/L]	-			-
relative standard deviation [%]	-			-

The mean measured concentration in 1-octanol was determined to be below the LOD of <13.22 mg/L.

To verify the accuracy of the analytical method two freshly prepared standard solutions (prepared with the test item) were measured in between the samples of the flask method.

Table 4: Measurement of standard solutions

Standard solution (nominal value [mg/L])	Measured value [mg/L]	Recovery rate [%]
Standard-Ü1 (117.4)	117.9	100.4
	118.3	100.8
Standard-Ü2 (108.6)	108.2	99.6
	106.8	98.3

The recovery rate of the measured standard solutions was in the range from 98.3 % to 100.8 % which shows a very good accuracy of the analytical method.

The water solubility of the test item was determined to be 517 g/L. The 1-octanol solubility was determined to be <13.22 mg/L. Thus, the partition coefficient of the test item is calculated to be

Pow = <2.56 x 10^-5
log Pow = < -4.59

Conclusions:

The partition coefficient at 20 °C of the test item was calculated from the solubilities of the test item in water and 1-octanol to be:
Pow = < 2.56E-5 and log Pow = < -4.59

Executive summary:

A study was conducted in accordance with OECD TG 107 and Regulation (EC) No 440/2008 method A.8 to determine the partition coefficient of the test substance. With the estimated range of the water solubility of the test item estimated in the preliminary test (1061 - 2318 g/L) and the estimated solubility in 1-octanol (<0.2201 g/L), the partition coefficient can be estimated to be <-2. Therefore, the partition coefficient was calculated from the solubilities of the test item in 1-octanol and water. The water and 1-octanol samples were analysed using HPLC. The water solubility of the test item was determined to be 517 g/L. The 1-octanol solubility was determined to be <13.22 mg/L. Thus, the partition coefficient of the test item is calculated to be Pow = <2.56E-5 and the log Pow = <-4.59.

Description of key information

The partition coefficient at 20 °C of the test item was calculated from the solubilities of the test item in water and 1-octanol to be: Pow = < 2.56E-5 and log Pow = < -4.59 (reference 4.7-1)

Additional information

A study was conducted in accordance with OECD TG 107 and Regulation (EC) No 440/2008 method A.8 to determine the partition coefficient of the test substance. With the estimated range of the water solubility of the test item estimated in the preliminary test (1061 - 2318 g/L) and the estimated solubility in 1-octanol (<0.2201 g/L), the partition coefficient can be estimated to be <-2. Therefore, the partition coefficient was calculated from the solubilities of the test item in 1-octanol and water. The water and 1-octanol samples were analysed using HPLC. The water solubility of the test item was determined to be 517 g/L. The 1-octanol solubility was determined to be <13.22 mg/L. Thus, the partition coefficient of the test item is calculated to be Pow = <2.56E-5 and the log Pow = <-4.59.