L-Glutamic acid, N-acetyl-, compd. with (.alpha.S)-.alpha.-(2-methylpropyl)-2-(1-piperidinyl)benzenemethanamine (1:1)

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 June 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted in accordance with several internationally established guidelines (OECD, EEC, EPA guidelines, see below).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

(S)-3-Methyl-1-(2-piperidine-1-phenyl)butylamine compound with N-Acetyl-L-glutamic acid

EC Number:

606-883-4

Cas Number:

219921-94-5

Molecular formula:

C16-H26-N2 x C7-H11-N-O5

IUPAC Name:

(S)-3-Methyl-1-(2-piperidine-1-phenyl)butylamine compound with N-Acetyl-L-glutamic acid

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): AGEE 623 Glutaminate; L-Glutamic acid, N-acetyl, compd. with (S)-alpha-(2-methylpropyl)-2-(1-piperidinyl)-benzenemethanamine
- Physical state: solid white powder
- Analytical purity: 100% measured over area (4% of (R)-(-)-enantiomer
- Lot/batch No.: T29725
- Expiration date of the lot/batch: 31 december 1999
- Stability under test conditions: pure: see expiry date
- Storage condition of test material: in original container, at room temperature, in the dark

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Type:

log Pow

Partition coefficient:

> 6

Temp.:

20 °C

Any other information on results incl. tables

HPLC Method

The solution of the test substance was injected five times and the solution of the reference compounds were injected five times each at one concentration level. Based on the chromatographic data, AGEE 623 Glutaminate was considered to be stable during the test procedure.

The partition coefficient was calculated based on a calibration curve using 7 reference compounds. The difference between the five measurements of the reference mixture is less than the given limit of 0.1 log P units, therefore the study is considered to be valid.

The temperature of the mobile phase was thermostated to 20°C +-1°C during the HPLC measurement.

The linearity of the analytical method was proved in the log P_ow range from 1.9 to 5.7.

The chromatograms obtained for the sample solution show that the partition coefficient of AGEE 623 Glutaminate was determined to be log P_ow > 6.

Additional to the procedure as described above, further measurements were performed to confirm the results obtained. The sample solution of AGEE 623 Glutaminate and the triphenylamine reference solution were measured by HPLC analysis using 100% acetonitrile as mobile phase for the elution. The higher retention time measured for AGEE 623 Glutaminate proved that the partition coefficient of the test substance AGEE 623 Glutaminate was determined to be log P_ow > 6

Applicant's summary and conclusion

Conclusions:

The partition coefficient (n-Octanol / Water) of AGEE 623 Glutaminate was determined to be log Pow > 6 at 20°C.