N,N'-[dithiobis[2-(2-hydroxyethyl)-1-methylvinylene]]bis[N-[(4-amino-2-methyl-5-pyrimidinyl)methyl]formamide

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - HPLC Method)

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:

N,N'-[dithiobis[2-(2-hydroxyethyl)-1-methylvinylene]]bis[N-[(4-amino-2-methyl-5-pyrimidinyl)methyl]formamide

EC Number:

200-644-4

EC Name:

N,N'-[dithiobis[2-(2-hydroxyethyl)-1-methylvinylene]]bis[N-[(4-amino-2-methyl-5-pyrimidinyl)methyl]formamide

Cas Number:

67-16-3

Molecular formula:

C24H34N8O4S2

IUPAC Name:

N,N'-[dithiobis[2-(2-hydroxyethyl)-1-methylvinylene]]bis[N-[(4-amino-2-methyl-5-pyrimidinyl)methyl]formamide

Test material form:

solid: particulate/powder

Remarks:

Pale yellow powder

Details on test material:

Batch : 18117240
Dose calculation will not be adjusted to purity

Specific details on test material used for the study:

Batch 14/10/GP2
Expiry date : 10/09/2012
Storage : room temperature 20°C +/-5°C - dark - dry

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

< 0.3

Temp.:

20 °C

pH:

ca. 5

Any other information on results incl. tables

CONDUCT OF THE STUDY

-Pre-Tests:

In the preliminary test, a solution of the test item with a concentration of 1060 mg/l was injected in order to check retention time and the signal height

-Determination of Dead Time:

The dead time to was measured by using an unretained organic compound (thio urea) which was included in the mix of the reference items.

-Determination of the Log Pow of the Test Item:

A mix of reference items (with toluene as substance with the highest log POW) and a test item solution with a concentration of 1060 mg/L was used for the determination of the log Pow of the test item.

One vial was filled with the reference item mix and one vial with the test item solution. The vials were analysed using the HPLC. Three injections were measured from the reference item mix, three injections from the test item and again  three injections from the reference item mix.

 

The data was saved, the retention times of the seven peaks of the reference item mix andthe retention time of the peak of the test item were used for further calculations.

 

CALCULATION OF RESULT:

Capacity Factor K :

The capacity factor K for every peak was calculated using the following equation: K = (tR-t0)/t0

with

tR: retention time,

t0: dead time

 

Calibration Log K vs Log Pow

The calibration function was drawn up from the six measurements of the capacity factors of the reference items. By plotting the log Pow values (as stated in the guideline) of the reference items against the mean log capacity factors and performing linear regression, a calibration function was obtained.

 

Calibration of Log Pow :

With the calculated capacity factors for the test item, each log Pow from the three determinations was calculated.

Finally, mean and standard deviation of the log Pow were calculated.

Applicant's summary and conclusion

Conclusions:

The chromatogram of the test item 5007 TDS gave one peak with the mean retention time of 1.706 minutes. With the calibration function log K versus log Pow, the corresponding log Pow was calculated. Because the peak lies within the dead time of the method and not within the range of log Pows of the reference items, the log Pow of the test item 5007 TDS should be stated as <0.3.