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

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

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 105 (Water Solubility)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Key result

Water solubility:

517 g/L

Conc. based on:

test mat.

Incubation duration:

>= 24 - <= 72 h

Temp.:

20 °C

pH:

>= 7.1 - <= 7.2

Preliminary Test

The preliminary test at room temperature showed, that the water solubility of the test item was >1061 g/L.

 

Table 2: Preliminary test for the water solubility

Amount of test item [mg]	Added volume of water [mL]	Ultrasonic bath [min]	Remark
104.48	0.1	-	not dissolved
	0.6	-	dissolved
106.09	0.1	2	dissolved

The solubility of the test item in water at room temperature was estimated to be >1061 g/L. Therefore, the flask method was performed.

Main Test (flask method)

For the main test three flasks were prepared with an amount of test item and water, and one flask only with water. After stirring and centrifugation the aqueous 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	4 a
measured value [mg/L]	408.3 / 409.7	408.9 / 406.4	426.2 / 422.3	0 / 0
aliquot of the flask [mL]	1	1	1	1
total volume after 1^st dilution [mL]	50	50	50	50
aliquot of the 1^st dilution [mL]	1	1	1	1
total volume after 2^nd dilution [mL]	25	25	25	25
water solubility [g/L]*	510.3 / 512.1	511.2 / 508.0	532.8 / 527.9	0 / 0
average water solubility [g/L]	511.2	509.6	530.3	0
mean value of the water solubility [g/L]	517.0			0
standard deviation [g/L]	11.5			-
relative standard deviation [%]	2.2			-

* Under consideration of the dilution factor 1250.

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 (410.2)	408.2	99.5
	410.2	100.0
Standard-Ü2 (390.8)	392.4	100.4
	392.7	100.5

The recovery rate of the measured standard solutions was in the range from 99.5 % to 100.5 % which shows a very good accuracy of the analytical method.

Conclusions:

The water solubility of the test item at 20 °C and pH 7.1 to be 517.0 g/L.

Executive summary:

The water solubility was determined according to OECD 105 and Regulation (EC) No. 440/2008 method A.6 using the shake flask method with HPLC analysis. About 45 g test item were weighed into flasks according to the estimated solubility based on the Preliminary Test. After the addition of 25 mL ultra-pure water, the flasks were agitated at 30 °C. After stirring at 30 °C, the flasks were cooled down to 20 °C and stirred at 20 °C for at least another 24 h. After 24 h stirring time, the contents of the flasks were centrifuged for 30 min at 20 °C with 15000 rpm. The samples were diluted before the analysis (two parallel dilutions). The pH of each sample was recorded. The water solubility of the test substance was determined to be 517 g/L at 20 °C (pH = 7.1 – 7.2).

Description of key information

The water solubility of the test item at 20 °C and pH 7.1 to be 517.0 g/L (reference 4.8-1).

Key value for chemical safety assessment

Water solubility:

517 g/L

at the temperature of:

20 °C

Additional information

The water solubility was determined according to OECD 105 and Regulation (EC) No. 440/2008 method A.6 using the shake flask method with HPLC analysis. About 45 g test item were weighed into flasks according to the estimated solubility based on the Preliminary Test. After the addition of 25 mL ultra-pure water, the flasks were agitated at 30 °C. After stirring at 30 °C, the flasks were cooled down to 20 °C and stirred at 20 °C for at least another 24 h. After 24 h stirring time, the contents of the flasks were centrifuged for 30 min at 20 °C with 15000 rpm. The samples were diluted before the analysis (two parallel dilutions). The pH of each sample was recorded. The water solubility of the test substance was determined to be 517 g/L at 20 °C (pH = 7.1 – 7.2).