D-threo-Pentitol, 2,5-anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4-[[4-[4-[4-[[[1-[(1S,2S)-1-ethyl-2-(phenylmethoxy)propyl]hydrazino]carbonyl]amino]phenyl]-1-piperazinyl]phenoxy]methyl]-1-(1H-1,2,4-triazol-1-yl)-

Partition coefficient

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Version / remarks:

(2008)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2004)

Deviations:

no

Test guideline 3

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

Test material information

Constituent 1

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 coefficient

Partition coefficient 1

Type:

log Pow

Partition coefficient:

3.6

pH:

2

Remarks on result:

other: Pow= 3.8 E+3

Partition coefficient 2

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.