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Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Given the purity of the test substance is not stated the reliability is with restrictions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Version / remarks:
(adopted March 30, 1989)
Qualifier:
according to guideline
Guideline:
EU Method A.8 (Partition Coefficient)
Version / remarks:
(December 1992)
GLP compliance:
not specified
Type of method:
HPLC method
Partition coefficient type:
octanol-water

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(3,5-Dihydroxyphenyl)-1-oxo-2-(N-1-(4-methoxyphenyl)isopropylamino)ethane Hydrobromide
EC Number:
928-779-0
Molecular formula:
C18-H21-N-O4 x HBr
IUPAC Name:
1-(3,5-Dihydroxyphenyl)-1-oxo-2-(N-1-(4-methoxyphenyl)isopropylamino)ethane Hydrobromide
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Using a computer calculation program, the pKa values of the substance were calculated to be 5.1 (basic group) and 9.3 and 11.3 (both acidic groups). Based on this, it was decided to buffer the mobile phase at pH=8.

Study design

Analytical method:
high-performance liquid chromatography

Results and discussion

Partition coefficientopen allclose all
Key result
Type:
log Pow
Partition coefficient:
1.1
Temp.:
24.5 °C
pH:
8
Remarks on result:
other: major component
Type:
Pow
Partition coefficient:
11
Temp.:
24.5 °C
pH:
8
Remarks on result:
other: major component
Type:
log Pow
Partition coefficient:
< 0.3
Temp.:
24.5 °C
pH:
8
Remarks on result:
other: minor component (impurities)
Type:
Pow
Partition coefficient:
< 2
Temp.:
24.5 °C
pH:
8
Remarks on result:
other: minor component (impurities)

Any other information on results incl. tables

Determination of pKa values

Using a computer calculation program, the pKa values of the test substance were calculated to be 5.1 (basic group) and 9.3 and 11.3 (both acidic groups). Based on this, it was decided to buffer the mobile phase at pH=8.

HPLC method

In the HPLC chromatograms of the test substance, using detection at 210 nm, one large and two small test substance peaks were observed. It was assumed that the large peak derives from the major component of test substance whereas the small peaks derive from impurities. The first small peak eluted before the unretarded component.

The t0 was determined to be 0.959 minutes as a mean value of both measurements (i. e. 0.956 and 0.962 minutes). The mean values of the retention times, k' values, log k' values, log Pow and Pow values are summarized in table 1.

Table 1 Results of the test

 Substance  tr1  k'  log k'  log Pow  Pow
 Reference substance          
 Ethylmethylketone  1.76  0.832  -0.080  0.3  
 Nitrobenzene  5.95  5.200  0.716  1.9  
 Toluene  13.55  13.13  1.11  2.7  
 Bromobenzene  16.33  16.03  1.20  3.0  
 1,4 -dichlorobenzene  25.88  25.99  1.41  3.4  
 Biphenyl  40.68  41.42  1.62  4.0  
 Test substance          
 peak 1  0.863  n.a.  n.a.  <0.32  <2.0*100
 peak 2  1.01  0.053  -1.27  <0.32  <2.0*100
 peak 3 (major component)  2.89  2.017  0.30  1.13  1.1*101

1 Mean value of the retention times of both chromatograms.

2 Extrapolated from the regression line: log k' = 0.465 log Pow - 0.188 (r=0.998, n=6)

3 Interpolated from the regression line: log k' = 0.465 log Pow - 0.188 (r=0.998, n=6)

n.a. not applicable

Applicant's summary and conclusion

Conclusions:
The partition coefficient (n-octanol/water) of the major component of the test substance at 24.5 +- 0.5°C is 11 (log Pow = 1.1) and the partition coefficients (n-octanol/water) of the minor components of the test substance are < 2 (log Pow = <0.3) at 24.5 +- 0.5°C).