(4-amino-1-hydroxy-1-phosphonobutyl)phosphonic acid;hydrate

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-01-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

Deviations:

not applicable

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

sodium;(4-amino-1-hydroxy-1-phosphonobutyl)-hydroxyphosphinate

Cas Number:

121268-17-5

Molecular formula:

C4H12NaNO7P2 · 3 H2O

IUPAC Name:

sodium;(4-amino-1-hydroxy-1-phosphonobutyl)-hydroxyphosphinate

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: sponsor and 005Y030

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Not soluble in either the Sodium Borate buffer and the FMOC derivitizing agent

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Dissolved into a stock solution of 0.01 mol Alendronate Sodium / L octanol saturated water.
- Final dilution of a dissolved solid, stock liquid or gel: 1:1, 1:2, 2:1 ratios of water to octanol solutions were prepared from the stock solution to a quanitity of 15 mL

FORM AS APPLIED IN THE TEST (if different from that of starting material)
1:1, 1:2, 2:1 ratios of water to octanol solutions, each containing 3,250 mg Alendronate Sodium / L, were preapred in triplicate.

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Partition coefficient 1

Key result

Type:

Pow

Partition coefficient:

ca. 0.019

Temp.:

22.5 °C

pH:

ca. 5

Partition coefficient 2

Key result

Type:

log Pow

Partition coefficient:

ca. -1.73

Temp.:

22.5 °C

pH:

ca. 5

Details on results:

The octanol/water partition coefficient of Alendronate Sodium® was determined by analyzing the concentration of the test substance in the water phase after the samples reached partition equilibration. Alendronate Sodium® peaks were present in the water portion sample chromatographs. However, the
concentration in the octanol portion was inferred as the difference between the known concentration of test substance administered to the vessels prior to mechanical shaking, and the actual value of the test substance obtained in the analysis of the water phase.
The estimated Pow at a 1:1 octanol to water ratio ranged from 0.010 to 0.020, with a mean of 0.015 and a standard deviation of 0.005. The estimated Pow at a 1:2 octanol to water ratio ranged from 0.018 to 0.028, with a mean of 0.023 and a standard deviation of 0.005. The estimated Pow at a 2:1 octanol to water ratio ranged from 0.013 to 0.023, with a mean of 0.018 and a standard deviation of 0.005. The estimated log Pow values ranged from -1.64 to -1.82. This fulfilled the requirement that the log Pow values fall within± 0.3 units.

Applicant's summary and conclusion

Conclusions:

This study met the criteria to validly determine the octanol/water partition coefficient of the test substance according to the noted guideline.