2,2-bis({[3-(4-ethylpiperazin-1-yl)propanoyl]oxy}methyl)butyl 3-(4-ethylpiperazin-1-yl)propanoate

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

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)

Deviations:

no

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:

2,2-bis({[3-(4-ethylpiperazin-1-yl)propanoyl]oxy}methyl)butyl 3-(4-ethylpiperazin-1-yl)propanoate

EC Number:

700-404-3

Cas Number:

127929-37-7

Molecular formula:

C33H62N6O6

IUPAC Name:

2,2-bis({[3-(4-ethylpiperazin-1-yl)propanoyl]oxy}methyl)butyl 3-(4-ethylpiperazin-1-yl)propanoate

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Type:

log Pow

Partition coefficient:

>= 0.463 - <= 0.467

Temp.:

22 °C

pH:

>= 5.4 - <= 5.5

Any other information on results incl. tables

The chromatogram of the test item gave 10 peaks. With the help of the calibration function log K versus log Pow, the corresponding log Pows were determined as:

Peak	Mean retention time (min)	Log Pow (Mean +-sd)
1	1.128	-1.842 (+-0.093)
2	1.638	0.465 (+-0.002)
3	2.152	1.069 (+-0.000)
4	2.599	1.391 (+-0.006)
5	2.902	1.559 (+-0.005)
6	3.127	1.666 (+-0.003)
7	4.115	2.030 (+-0.028)
8	6.018	2.480 (+-0.003)
9	6.752	2.608 (+-0.003)
10	7.902	2.778 (+-0.003)

Peak 2 shows much larger areas than the other peaks. Although area is not necessarily correlated to absolute concentration if a UV detector is used, it is believed that the test item B 1061 consists mainly of this main peak, indicating, that the log Pow of the test item should be regarded as approx. 0.465.

As the first peak of the test item lies outside the range of the reference items, the log Pow of this peak should be stated as < 0.3 (log Pow of the first reference item).

Applicant's summary and conclusion

Conclusions:

Peak 2 shows much larger areas than the other peaks. Although area is not necessarily correlated to absolute concentration if a UV detector is used,
it is believed that the test item B 1061 consists mainly of this main peak, indicating, that the low Pow of the test item schould be regarded as approx.
0.465.

Executive summary:

The study was performed using a HPLC with a C18 column. Seven reference items with different retention times were used to produce a calibration curve, since retention time on hydrophobic columns and Pow are correlated. The reference items were chosen on behalf of the retention time of the test item on the column.

First, a solution of the reference items was analysed with HPLC, then a solution of the test item, and finally again the solution with the reference items. Each analysis was performed three times. For each reference item, the capacity factor K was calculated from the retention time of thio urea and the retention time of the respective reference item. A calibration function (log K versus log Pow, linear fit) was determined using the literature values for log Pow of the reference items and mean log K of the six determinations. The chromatogram of the test item gave 10 peaks. With the help of the calibration function log K versus log Pow, the corresponding log Pows were determined.

Peak 2 shows much larger areas than the other peaks. Although area is not necessarily correlated to absolute concentration if a UV detector is used, it is believed that the test item B 1061 consists mainly of this main peak, indicating, that the low Pow of the test item schould be regarded as approx. 0.465.