Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 March 2012- 11 July 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and EC guidelines and according to the principles of GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method A.8 (Partition Coefficient)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Version / remarks:
(2004)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)
Version / remarks:
(1996)
Deviations:
no
GLP compliance:
yes
Type of method:
HPLC method
Remarks:
The HPLC method was performed at pH 2 and at pH 8.
Partition coefficient type:
octanol-water

Test material

Constituent 1
Chemical structure
Reference substance name:
2,5-anhydro-4-{[4-(4-{4-[({1-[(2S,3S)- 2-(benzyloxy)pentan-3-yl]hydrazino}carbonyl)amino]phenyl}piperazin1-yl)phenoxy]methyl}-1,3,4-trideoxy-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-
EC Number:
701-059-1
Cas Number:
345217-03-0
Molecular formula:
C43H50F2N8O4
IUPAC Name:
2,5-anhydro-4-{[4-(4-{4-[({1-[(2S,3S)- 2-(benzyloxy)pentan-3-yl]hydrazino}carbonyl)amino]phenyl}piperazin1-yl)phenoxy]methyl}-1,3,4-trideoxy-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): PAZ-D
- Physical state: white powder
- Hygroscopic

Results and discussion

Partition coefficientopen allclose all
Type:
log Pow
Partition coefficient:
3.6
pH:
2
Remarks on result:
other: Pow= 3.8 E+3
Type:
log Pow
Partition coefficient:
4.9
pH:
8
Remarks on result:
other: Pow= 8.6 E+4
Details on results:
In each of the HPLC chromatograms (pH 2 and pH 8) of the test solutions, one test substance peak was observed.

Any other information on results incl. tables

Table: Test resultsat pH 2

 

Substance

tr,1
[min]

tr,2
[min]

mean tr
(n=2)

log Pow

Pow

 

 

 

 

 

 

Formamide (t0)

1.142

1.140

1.141

 

 

Benzylalcohol

1.397

1.395

1.396

1.1

 

Nitrobenzene

1.788

1.786

1.787

1.9

 

Toluene

2.840

2.838

2.839

2.7

 

Bromobenzene

2.983

2.981

2.982

3.0

 

1,4-Dichlorobenzene

3.611

3.608

3.610

3.4

 

Biphenyl

4.751

4.748

4.750

4.0

 

 

 

 

 

 

 

Test substance

4.092

4.094

4.093

3.6

3.8 E3

 

Table: Test results at pH 8

 

Substance

tr,1
[min]

tr,2
[min]

mean tr
(n=2)

log Pow

Pow

 

 

 

 

 

 

Formamide (t0)

1.103

1.104

1.104

 

 

1,4-Dichlorobenzene

3.707

3.712

3.710

3.4

 

Biphenyl

4.920

4.927

4.924

4.0

 

1,2,4-Trichlorobenzene

5.842

5.850

5.846

4.2

Dibenzyl

7.251

7.263

7.257

4.8

 

Fluoranthene

10.307

10.324

10.316

5.1

 

Triphenylamine

11.130

11.154

11.142

5.7

 

 

 

 

 

 

 

Test substance

8.107

8.110

8.109

4.9

8.6 E4

 

Applicant's summary and conclusion

Conclusions:
The HPLC method was performed to determine the partition coefficient (n-octanol/water) at pH 2 and pH 8. At pH 8 the substance is >99% non-ionised, at pH 2 the substance is ionised for >90%. The HPLC chromatogram of the test solution showed one test substance peak; log Pow= 3.6 (at pH 2) and log Pow=4.9 (at pH 8). The study was performed in accordance with EC A.8, OECD 117 and EPA OPPTS 830.7570 guidelines and according to the principles of GLP.