Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 831-973-7 | CAS number: 147116-67-4
Partition coefficient
Administrative data
- Endpoint:
- partition coefficient
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- The experimental start date was 14 May 2019, and the experimental completion date was 16 May 2019.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: EC Guideline A.8.
- Version / remarks:
- Partition Coefficient. March 04, 2016.
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EC Guideline A.24.
- Version / remarks:
- Partition Coefficient (n-octanol/water), High Performance Liquid Chromatography (HPLC) Method. March 04, 2016.
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
- Version / remarks:
- Partition Coefficient (n-octanol/water), Shake Flask Method.
July 27, 1995. - Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
- Version / remarks:
- Partition Coefficient (n-octanol/water), High Performance Liquid
Chromatography (HPLC) Method. April 13, 2004. - Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 830.7550 (Partition Coefficient, n-octanol / H2O, Shake Flask Method)
- Version / remarks:
- Partition Coefficient (n-octanol/water), Shake Flask Method. August 1996
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)
- Version / remarks:
- Partition Coefficient (n-octanol/water), Estimation by Liquid Chromatography. August 1996.
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of method:
- HPLC method
- Partition coefficient type:
- octanol-water
Test material
- Reference substance name:
- (2S,3S)-2-benzhydryl-N-[(5-tert-butyl-2-methoxy-phenyl)methyl]quinuclidin-3-amine
- EC Number:
- 831-973-7
- Cas Number:
- 147116-67-4
- Molecular formula:
- C32H40N2O
- IUPAC Name:
- (2S,3S)-2-benzhydryl-N-[(5-tert-butyl-2-methoxy-phenyl)methyl]quinuclidin-3-amine
- Test material form:
- solid
- Details on test material:
- White to off-white powder.
Storage Conditions: At room temperature.
Constituent 1
- Specific details on test material used for the study:
- Batch (Lot) Number: 334115
Expiry date: 14 April 2020 (retest date)
Physical Description: White to off-white powder
Purity/Composition: 99.9%
Storage Conditions: At room temperature
Study design
- Analytical method:
- high-performance liquid chromatography
Results and discussion
Partition coefficientopen allclose all
- Key result
- Type:
- log Pow
- Partition coefficient:
- ca. 3.1
- pH:
- ca. 2
- Remarks on result:
- other: Temperature not specified
- Key result
- Type:
- Pow
- Partition coefficient:
- ca. 1 100
- pH:
- ca. 2
- Remarks on result:
- other: Temperature not specified
- Key result
- Type:
- log Pow
- Partition coefficient:
- >= 7.2
- pH:
- ca. 7.5
- Remarks on result:
- other: Temperature not specified
- Key result
- Type:
- Pow
- Partition coefficient:
- >= 16 000 000
- pH:
- ca. 7.5
- Remarks on result:
- other: Temperature not specified
Any other information on results incl. tables
PowCalculation
The Powof the test item was calculated to be 3.1x109(log Pow8.5) using the Rekker calculation method.
pKaValues
The pKavalues in the logarithm range of 1 - 14 for acidic and basic groups in the molecular structure of the test item were calculated using the Perrin calculation method. The results are given in Table 5. According to these calculations, testing of the non-ionised form would require a pH of≥12.8. The HPLC method cannot be performed at such high pH. As an alternative, it was decided to test at pH 2 in order to have the test item fully ionised and at pH 7.5 where the test item is singly charged.
Table 5
pKa Values of the Test Item
Acidic |
Basic |
|
- |
SUBST.-QUINUCLIDINE |
pKa10.8 |
RRNH2+ |
pKa5.9 |
|
HPLC Method
pH 2
UPLC-UV chromatograms of the test item solution and corresponding blank are shown inFigure 4 and Figure 5, respectively. In the chromatogram of the test solution, one major test item peak was observed.
The results of the HPLC method are given in theTable 6. Figure 6shows the calibration curve of the log k’ of the reference substances as function of log Pow. The equation of the regression line was: log k’ = 0.365´log Pow– 0.903 (r = 0.993, n = 12).
Table 6
pH 2: Powof the Test Item
Substance |
Retention time (min) |
log Pow |
Pow |
||
tr,1 |
tr,2 |
mean |
|||
Formamide (t0) |
0.608 |
0.612 |
0.610 |
|
|
Benzylalcohol |
0.788 |
0.787 |
|
1.1 |
|
Nitrobenzene |
0.970 |
0.968 |
|
1.9 |
|
Toluene |
1.537 |
1.533 |
|
2.7 |
|
1,4-Dichlorobenzene |
1.982 |
1.976 |
|
3.4 |
|
Biphenyl |
2.649 |
2.642 |
|
4.0 |
|
1,2,4-Trichlorobenzene |
3.054 |
3.045 |
|
4.2 |
|
Test item – peak 1 |
1.606 |
1.594 |
1.600 |
3.1 |
1.1´103 |
pH 7.5
UPLC-UV chromatograms of the test item solution and the corresponding blank are shown inFigure 7andFigure 8, respectively. In the chromatogram of the test item solution, one peak with a retention time of 23.5 minutes was observed. The shoulder on the test item peak was also observed on the peak for benzo[ghi]perylene(log Pow= 7.2) which under the same analytical conditions, eluted at 17.4 minutes. Because the shoulder was observed for both the test item and the reference substance, it was considered to be due to the column used and not
to derive from another compound. It could be safely concluded that the log Powof the test item was > 7.2 (Pow > 1.6 x107).
Applicant's summary and conclusion
- Conclusions:
- The HPLC method at pH 2 and pH 7.5 was applied for the determination of the partition coefficient (Pow) of Maropitant base (CJ-11,972).
The Pow and log Pow values of the test item at pH 2 and pH 7.5 were:
pH 2 pH 7.5
Pow log Pow Pow log Pow
Test item – peak 1 1.1 x 10^3 3.1 > 1.6 x 10^7 > 7.2
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
