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Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19-12-2017 to 20-12-2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
other: Draft study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Version / remarks:
13 april 2004
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EU method A.24 "Partition Coefficient (N-OCTANOL/WATER), HIGH PERFORMANCELIQUID CHROMATOGRAPHY (HPLC) METHOD"
Version / remarks:
Commission Regulation (EU) 2016/266 of adopted 7 December 2015 amending Regulation EC No. 440/2008
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of method:
HPLC method
Partition coefficient type:
octanol-water

Test material

Constituent 1
Chemical structure
Reference substance name:
Pyrrolidine, 1-[2-[2-nitro-4-(phenylmethoxy)phenyl]ethenyl]-
Cas Number:
99474-22-3
Molecular formula:
C19H20N2O3
IUPAC Name:
Pyrrolidine, 1-[2-[2-nitro-4-(phenylmethoxy)phenyl]ethenyl]-
Specific details on test material used for the study:
- Analytical purity: > 98.4%
- Lot/batch No.: 0159115
- Expiration date of the lot/batch: 21/02/2018

Study design

Analytical method:
high-performance liquid chromatography

Results and discussion

Partition coefficient
Key result
Type:
log Pow
Partition coefficient:
ca. 2.8
Temp.:
25 °C
pH:
ca. 7

Any other information on results incl. tables

Findings and Results

Reference Items

Measurement Data

 

The retention times which were recorded for the reference items are presented in the following table.

Table9.1‑a     Retention Times (RT) Reference Items

Compound

RT 1

RT 2

RT 3

RT 4

RT 5

RT 6

 

min.

min.

min.

min.

min.

min.

Thiourea

1.440

1.440

1.440

1.440

1.440

1.440

2-Butanone

1.754

1.753

1.756

1.754

1.754

1.756

Benzylalcohol

1.907

1.906

1.907

1.903

1.903

1.904

Acetophenone

2.193

2.190

2.193

2.189

2.190

2.190

Nitrobenzene

2.440

2.440

2.440

2.433

2.434

2.436

Benzene

3.143

3.143

3.144

3.133

3.133

3.133

Toluene

4.266

4.263

4.266

4.240

4.242

4.243

Naphthalene

5.200

5.196

5.200

5.167

5.170

5.170

 

Calculated Values

 

For each reference item, the calculated capacity factors are presented in the following table.

Table9.1‑b     Capacity factors Reference Items

Compound


Retention Time

Mean

Retention Time
Standard
 Deviation

Retention Time
Relative
Standard Deviation

k

 

min.

min.

%

 

Thiourea

1.440

0.000

0.006

0.0000

2-Butanone

1.754

0.001

0.079

0.2185

Benzylalcohol

1.905

0.002

0.090

0.3229

Acetophenone

2.191

0.002

0.073

0.5215

Nitrobenzene

2.437

0.003

0.130

0.6925

Benzene

3.138

0.006

0.181

1.1794

Toluene

4.253

0.013

0.303

1.9540

Naphthalene

5.184

0.016

0.317

2.6001

 

log POW/ log k

 

The values for log k and log POWof the reference items are presented in the following table:

Table9.1‑c    log k and log POWof Reference Items

Compound

log k

log POW

2-Butanone

-0.6606

0.30

Benzylalcohol

-0.4909

1.10

Acetophenone

-0.2828

1.70

Nitrobenzene

-0.1595

1.90

Benzene

0.0717

2.10

Toluene

0.2909

2.70

Naphthalene

0.4150

3.60

 

Correlation Results

 

Dead time is 1.440 ± 0.000 minutes, with RSD (relative standard deviation) 0.006%.

 

The RSD of the retention times of the reference items lay all below 0.32 %.

 

Equation of the regression:

 

log k = 0.3628 * log POW– 0.8112

with a coefficient of determination r2= 0.944

 

Test Item

Measurement Data

 

The retention times of the test item are presented in the following table:

Table9.2‑a     Retention Times (RT) Test Item

Measurement

RT

 

min.

Measurement 1

3.697

Measurement 2

3.697

Measurement 3

3.697

Mean

3.697

Standard deviation

0.000

 

 

Calculated Values

 

The calculated values are presented in the following table:

Table9.2‑b     Capacity Factor, log Capacity Factor, log POWTest Item

Measurement

k

log k

log POW

Measurement 1

1.5677

0.1953

2.774

Measurement 2

1.5672

0.1951

2.773

Measurement 3

1.5674

0.1952

2.774

Mean

 

 

2.774

Relative Standard deviation

 

 

0.000

 

log POWwas calculated from the capacity factor as follows:

 

log POW= (log k + 0.8112) / 0.3628

 

Result and Validity

Result

 

The test item shows one peak. Using the correlation log k / log POW, the log POWof test item was calculated as 2.774 ± 0.000 (mean ± standard deviation). 

 

Validity

 

The validity criteria and results are presented in the following table:

Table9.3‑a     Validity Criteria and Results

Peak

Parameter

Criterion

Found

Assessment

1

Range (Max – Min. log POW)

< 0.1

0.000

valid

Value withinofItems

0.30 - 3.60

2.774

valid

 

Discussion

 

Variations in the retention times of reference items and test item are very small. Therefore, a stable configuration of the HPLC-column can be assumed.

The correlation log k/log POWis good: the coefficient of determination r2was calculated with 0.944. This value was considered as sufficiently high to use the calibration function for the determination of the log POWof the test item.

 

Using the correlation log k / log POW,the log POWof the test item was calculated as2.774 ± 0.000(mean ± standard deviation).

 

Therefore, the log POWof the test item is stated as2.8(mean)at a temperature of 25 ± 0.5 °C and a pH value of 7.

 

No observations were made which might cause doubts concerning the validity of the study outcome.

 

 

Applicant's summary and conclusion

Conclusions:
The chromatogram of the test item gave one peak. With the calibration function log k ver-sus log POW, the corresponding log POW of the peak was calculated with:
2.774 ± 0.000 (mean ± standard deviation).

Therefore, the log POW of the test item IMEXINE OBA/50 SEC is stated as 2.8 (mean) at a temperature of 25 ± 0.5 °C and a pH value of 7.
Executive summary:

A GLP compliant study has been conducted according to the OECD TG 117 guideline in order to determine the log Pow of the test item. The study was performed using a HPLC with a C18 column. Seven reference items with different retention times and thiourea for the determination of the dead time were used to produce a calibration curve, since retention time on hydrophobic columns and POW are correlated. The reference items were chosen based on the results of the pre-test.

 

Variations in the retention times of reference items and test item are very small. Therefore, a stable configuration of the HPLC-column can be assumed.

The correlation log k/log POWis good: the coefficient of determination r2was calculated with 0.944. This value was considered as sufficiently high to use the calibration function for the determination of the log POWof the test item.

 

Using the correlation log k / log POW,the log POWof the test item was calculated as2.774 ± 0.000(mean ± standard deviation).

 

Therefore, the log POWof the test item is stated as2.8(mean)at a temperature of 25 ± 0.5 °C and a pH value of 7.

 

No observations were made which might cause doubts concerning the validity of the study outcome.