Dihydronicotinamide-adenine dinucleotide, disodium salt

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 - 25 August 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

1995

Deviations:

yes

Remarks:

see principles of method if other than guideline

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

Regulation (EC) No 440/2008

Deviations:

yes

Remarks:

see principles of method if other than guideline

Principles of method if other than guideline:

Due to very high water solubility of the test item, estimated in a preliminary test, a modified TG OECD 105 design was conducted. Instead of equilibrating a large amount of test item with water by stirring over several days and subsequently separating the test item (about five times in excess) from the saturated solution, water was added in a stepwise procedure to a defined amount of test item until complete dissolution occurred.

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Test material

Test material information

Constituent 1

Reference substance name:

Dihydronicotinamide-adenine dinucleotide, disodium salt

EC Number:

210-123-3

EC Name:

Dihydronicotinamide-adenine dinucleotide, disodium salt

Cas Number:

606-68-8

Molecular formula:

C21H27N7O14P2.2Na

IUPAC Name:

disodium [(2R,3S,4R,5R)-5-(3-carbamoyl-1,4-dihydropyridin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl ({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphonato}oxy)phosphonate

impurity 1

Reference substance name:

Dihydronicotinamide-adenine dinucleotide

EC Number:

200-393-0

EC Name:

Dihydronicotinamide-adenine dinucleotide

Cas Number:

58-68-4

Molecular formula:

C21H29N7O14P2

IUPAC Name:

[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(3-carbamoyl-4H-pyridin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate

impurity 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Oxidane

Test material form:

solid: crystalline

Remarks:

crystaline powder

Details on test material:

Batch No.: 18243100
Storage conditions: Store at -15 to -25°C,
Handling: Keep frozen on dry ice.

Results and discussion

Water solubility

Key result

Water solubility:

>= 712 g/L

Conc. based on:

test mat. (dissolved fraction)

Temp.:

22.5 °C

pH:

7

Details on results:

Preliminary test
Approximately 0.1 g of the test item were completely dissolved in 0.2 mL of ultra-pure water indicating a water solubility of about 500-1000 g/L.

Main test
The results are given in the table in the next section. The water solubility was determined as the mean of the triplicate test assays analysed with HPLC. As this method does not ensure complete saturation of the solution, it is given as a minimum value in mass per volume of solution. The test is satisfactory, if the concentrations of the three vessels do not differ by more than 15%.

Any other information on results incl. tables

HPLC determinations:

Test vessel	pH	Analysed concentration A (g/L)	Analysed concentration B (g/L)	Mean (g/L)
No. 1	7	706	708	707
No. 2	7	720	718	719
No. 3	7	711	710	710
			Overall Mean	712

The concentrations of the three vessels differed by 2% (validity criterion given by OECD is met).

Further remarks

Based on the test item amount used (ca. 1 g) and the volume of ultra-pure water applied (0.8 ml) to achieve complete dissolution, a theoretical solubility of ca. =1250 g/l results, which is significantly higher than the water solubility determined in this test. It has to be considered in this case that the final volume of the test item solution is most likely higher than just the 0.8 ml of the ultra-pure water added, due to the very high test item concentrations.

Applicant's summary and conclusion

Conclusions:

The water solubility of beta-NADH, disodium salt (CAS no. 606-68-8) was determined according to a modified TG OECD 105 design.
The water solubility of the test item at 22.5°C was >=712 g/L. The pH of the aqueous samples was 7.

Executive summary:

The water solubility of beta-NADH, disodium salt (CAS no. 606-68-8) was determined according to a modified TG OECD 105 design.

To this end, increasing volumes of water were added in a stepwise procedure, to approximately 1 g of the test item at 22 ± 2 °C until complete dissolution, which occurred after addition of 0.8 mL of water. The concentration of test item was subsequently determined by HPLC with UV detection.

The determined water solubility of beta-NADH, disodium salt is >=712 g/L at pH 7 and at 22.5 °C.