4-benzyloxy-2-nitro-beta-pyrrolidinostyrene

Partition coefficient

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

13 april 2004

Deviations:

no

Test guideline 2

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

Test material information

Constituent 1

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 P_OW/ log k

 

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

Table9.1‑c    log k and log P_OWof 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 P_OW– 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 P_OWTest 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 P_OWwas calculated from the capacity factor as follows:

 

log P_OW= (log k + 0.8112) / 0.3628

 

Result and Validity

Result

 

The test item shows one peak. Using the correlation log k / log P_OW, the log P_OWof 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 P_OWis 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 P_OWof the test item.

 

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

 

Therefore, the log P_OWof 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 P_OWis 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 P_OWof the test item.

 

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

 

Therefore, the log P_OWof 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.