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EC number: - | CAS number: -
Partition coefficient
Administrative data
- Endpoint:
- partition coefficient
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- FROM 07 JAN 2021 TO 08 SEP 2022
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 022
- Report date:
- 2022
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EU Method A.8 (Partition Coefficient - HPLC Method)
- Version / remarks:
- November 2019
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: • EC Guideline A.24. Partition Coefficient (n-octanol/water) , High Performance Liquid Chromatography (HPLC) Method
- Version / remarks:
- November 2019
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
- Version / remarks:
- April 2004
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)
- Version / remarks:
- August 1996
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method A.23 Partition Coefficient (1-Octanol/Water): Slow-Stirring Method
- Version / remarks:
- November 2019
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 123 (Partition Coefficient (1-Octanol / Water), Slow-Stirring Method)
- Version / remarks:
- March 2006
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of method:
- slow-stirring method
Test material
- Reference substance name:
- N-[4-[4-[(dimethylamino)methyl]-3-phenyl-1H-pyrazol-1-yl]pyrimidin-2-yl]-6-methoxy-4-(morpholin-4-yl)benzene-1,3-diamine
- Cas Number:
- 1903009-56-2
- Molecular formula:
- C27H32N8O2
- IUPAC Name:
- N-[4-[4-[(dimethylamino)methyl]-3-phenyl-1H-pyrazol-1-yl]pyrimidin-2-yl]-6-methoxy-4-(morpholin-4-yl)benzene-1,3-diamine
- Test material form:
- solid: particulate/powder
1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Batch (Lot) Number: I20AD0249 and I20ID2980 *
- Purity/Composition: 99.3% (batch I20ID2980)
- Purity/Composition correction factor: 1.0
- Purity test date : 2020-10-26
- Expiry date: 21 January 2022 (retest date) for batch I20AD0249 and 17 September 2022 (retest date) for batch I20ID2980
- Physical Description: Beige powder
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
* Batch I20ID2980 was used from 07 Feb 2022 onwards. Two LC-MS/MS validations and partition coefficient study using HPLC method were performed with using batch I20AD0249. All other studies were performed with batch I20ID2980.
Study design
- Analytical method:
- high-performance liquid chromatography
Results and discussion
Partition coefficientopen allclose all
- Key result
- Type:
- log Pow
- Partition coefficient:
- 3.3
- Temp.:
- 24.6 °C
- pH:
- 7
- Remarks on result:
- other: log Dow
- Key result
- Type:
- log Pow
- Partition coefficient:
- 4.4
- Temp.:
- 25.4 °C
- pH:
- 11
- Details on results:
- pH 7
The analysed concentration of the spiking solution was 0.474 g/L which corresponded to a recovery of 96%. Recoveries per sampling point were determined according to this value.
No test material was detected in the samples from the blank mixture.
The pH of the blank samples was pH 7.0 and 7.1.
pH 11
The analysed concentration of the spiking solution was 0.451 g/L which corresponded to a recovery of 91%. Recoveries per sampling point were determined according to this value.
No test material was detected in the blank samples.
The pH of the blank samples was pH 11.0 and 11.1.
Any other information on results incl. tables
pH 7: Dow of the test material
Vessel | Sampling point | Date and time of sampling | Analysed concentration | Dow | log Dow | pH | |||
| 1-octanol | Buffer pH 7 | Recovery [%] |
| Individual | Mean |
| ||
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1 | 1 | 06-Jul-2022 07:20 1 | 0.449 | 0.000243 | 96 | 1.8 x 103 | 3.3 | 3.2 | 7.1 |
| 2 | 06-Jul-2022 12:23 1 | 0.492 | 0.000249 | 105 | 2.0 x 103 | 3.3 |
| 7.1 |
| 3 | 08-Jul-2022 07:33 | 0.344 | 0.000385 | 74 | 8.9 x 102 | 3.0 |
| 7.1 |
| 4 | 08-Jul-2022 13:10 | 0.483 | 0.000243 | 103 | 2.0 x 103 | 3.3 |
| 7.1 |
| 5 | 11-Jul-2022 08:07 | 0.478 | 0.000236 | 102 | 2.0 x 103 | 3.3 |
| 7.1 |
| 6 | 11-Jul-2022 13:13 | 0.473 | 0.000235 | 101 | 2.0 x 103 | 3.3 |
| 7.1 |
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2 | 1 | 06-Jul-2022 07:20 1 | 0.466 | 0.000250 | 99 | 1.9 x 103 | 3.3 | 3.3 | 7.1 |
| 2 | 06-Jul-2022 12:23 1 | 0.489 | 0.000246 | 104 | 2.0 x 103 | 3.3 |
| 7.1 |
| 3 | 08-Jul-2022 07:33 | 0.489 | 0.000250 | 104 | 2.0 x 103 | 3.3 |
| 7.1 |
| 4 | 08-Jul-2022 13:10 | 0.484 | 0.000243 | 103 | 2.0 x 103 | 3.3 |
| 7.1 |
| 5 | 11-Jul-2022 08:07 | 0.479 | 0.000240 | 102 | 2.0 x 103 | 3.3 |
| 7.1 |
| 6 | 11-Jul-2022 13:13 | 0.484 | 0.000235 | 103 | 2.1 x 103 | 3.3 |
| 7.1 |
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3 | 1 | 06-Jul-2022 07:20 1 | 0.479 | 0.000248 | 102 | 1.9 x 103 | 3.3 | 3.3 | 7.1 |
| 2 | 06-Jul-2022 12:23 1 | 0.480 | 0.000243 | 102 | 2.0 x 103 | 3.3 |
| 7.1 |
| 3 | 08-Jul-2022 07:33 | 0.496 | 0.000241 | 106 | 2.1 x 103 | 3.3 |
| 7.1 |
| 4 | 08-Jul-2022 13:10 | 0.500 | 0.000244 | 107 | 2.1 x 103 | 3.3 |
| 7.1 |
| 5 | 11-Jul-2022 08:07 | 0.461 | 0.000239 | 98 | 1.9 x 103 | 3.3 |
| 7.1 |
| 6 | 11-Jul-2022 13:13 | 0.466 | 0.000236 | 99 | 2.0 x 103 | 3.3 |
| 7.1 |
| 7 | 12-Jul-2022 11:58 2 | 0.439 | 0.000249 | 94 | 1.8 x 103 | 3.2 |
| 7.0 |
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| Mean log Dow 3 | 3.3 |
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| ||
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| Mean Dow 3 | 2.0 x 103 |
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| Average σ log Dow 3 | 3.7 x 10-3 |
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1 Sampling points were excluded from the calculations since there was a power failure in the night from 06 Jul 2022 to 07 Jul 2022.
2 Additional sampling took place since the initial calculation of the mean log Dow value with four time points yield a slope that is not significantly different
from zero at a p-level of 0.05
pH 7: Calculations of mean and σ Dow
| Vessel 1 | Vessel 2 | Vessel 3 | Average |
|
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|
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|
P value slope | 0.0640 | 0.00424 | -0.0127 |
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log Dow, i | 3.2 | 3.3 | 3.3 |
|
log Dow, av |
|
|
| 3.3 |
|
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|
Variance | 0.0232 | 0.0000638 | 0.000620 |
|
Weighting factor (wi) | 43.1 | 15671 | 1613 |
|
log Dow * weighting factor | 138 | 51732 | 5308 |
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log Dow, i - log Dow, av | -0.0857 | 0.00123 | -0.00961 |
|
wi * (log Dow, i - log Dow, av)2 | 0.317 | 0.0235 | 0.149 |
|
wi * (n-1) | 86 | 31342 | 4840 |
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var log Dow, av |
|
|
| 1.3 x 10-5 |
σ log Dow , av |
|
|
| 3.7 x 10-3 |
pH 11
pH 11: Pow of the test material
Vessel | Sampling point | Date and time of sampling | Analysed concentration | Pow | log Pow | pH | |||
| 1-octanol | Water pH 11 | Recovery [%] |
| Individual | Mean |
| ||
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1 | 1 | 05-Sep-2022 08:381 | 0.412 | 0.000015 | 91 | 2.8 x 104 | 4.4 | 4.4 | 11.0 |
| 2 | 05-Sep-2022 14:28 1 | 0.474 | 0.000016 | 105 | 2.9 x 104 | 4.5 |
| 11.1 |
| 3 | 06-Sep-2022 07:35 1 | 0.502 | 0.000017 | 111 | 2.9 x 104 | 4.5 |
| 11.0 |
| 4 | 06-Sep-2022 13:33 1 | 0.509 | 0.000032 | 113 | 1.6 x 104 | 4.2 |
| 11.0 |
| 5 | 08-Sep-2022 07:25 | 0.522 | 0.000016 3 | 116 | 3.2 x 104 | 4.5 |
| 11.1 |
| 6 | 08-Sep-2022 13:19 | 0.513 | 0.000035 | 114 | 1.5 x 104 | 4.2 |
| 11.1 |
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2 | 1 | 05-Sep-2022 08:381 | 0.475 | 0.000016 | 105 | 3.0 x 104 | 4.5 | 4.4 | 11.0 |
| 2 | 05-Sep-2022 14:28 1 | 0.473 | 0.000017 | 105 | 2.8 x 104 | 4.5 |
| 11.1 |
| 3 | 06-Sep-2022 07:35 1 | 0.513 | 0.000018 | 114 | 2.9 x 104 | 4.5 |
| 11.0 |
| 4 | 06-Sep-2022 13:33 1 | 0.504 | 0.000034 | 112 | 1.5 x 104 | 4.2 |
| 11.0 |
| 5 | 08-Sep-2022 07:25 | 0.536 | 0.000020 | 119 | 2.7 x 104 | 4.4 |
| 11.2 |
| 6 | 08-Sep-2022 13:19 | 0.522 | 0.000031 | 116 | 1.7 x 104 | 4.2 |
| 11.1 |
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3 | 1 | 05-Sep-2022 08:381 | 0.441 | 0.000015 | 98 | 3.0 x 104 | 4.5 | 4.4 | 11.1 |
| 2 | 05-Sep-2022 14:28 1 | 0.470 | 0.000016 | 104 | 2.9 x 104 | 4.5 |
| 11.1 |
| 3 | 06-Sep-2022 07:35 1 | 0.505 | 0.000019 | 112 | 2.6 x 104 | 4.4 |
| 11.0 |
| 4 | 06-Sep-2022 13:33 1 | 0.511 | 0.000034 | 113 | 1.5 x 104 | 4.2 |
| 11.0 |
| 5 | 08-Sep-2022 07:25 | 0.519 | 0.000019 | 115 | 2.7 x 104 | 4.4 |
| 11.2 |
| 6 | 08-Sep-2022 13:19 | 0.514 | 0.000032 | 114 | 2.7 x 104 | 4.4 |
| 11.2 |
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| Mean log Pow 4 | 4.4 |
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| Mean Pow 4 | 2.4 x 104 |
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| Average σ log Pow 4 | 7.2 x 10-1 |
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1 Due to the system problems samples were analyzed on 07 Sep 2022. They were stored in the autosampler until analysis. Due to that additional samples
were taken on 08 Sep 2022.
2 Estimated values calculated by extrapolation of the calibration curve.
3 Result after re-dilution. Initially the sample was wrongly diluted.
pH 11: Calculations of mean and σ Pow
| Vessel 1 | Vessel 2 | Vessel 3 | Average |
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P value slope | -0.0416 | -0.0455 | -0.00366 |
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log Pow, i | 4.4 | 4.4 | 4.4 |
|
log Pow, av |
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| 4.4 |
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Variance | 0.0184 | 0.0154 | 0.0102 |
|
Weighting factor (wi) | 54.3 | 65.0 | 98.3 |
|
log Pow * weighting factor | 238 | 284 | 432 |
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log Pow, i - log Pow, av | -1.62 | -1.63 | -1.60 |
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wi * (log Pow, i - log Pow, av)2 | 143 | 173 | 252 |
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wi * (n-1) | 272 | 325 | 491 |
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var log Pow, av |
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| 5.2 x 10-1 |
σ log Pow , av |
|
|
| 7.2 x 10-1 |
Applicant's summary and conclusion
- Conclusions:
- The slow-stirring method at pH 7 and pH 11 was applied for the determination of the partition coefficient/distribution coefficient (Pow / Dow) of JNJ-73848281-AAA (T003904).
The Pow /Dow and log Pow /log Dow values of the test material at pH 7 and pH 11 were:
pH 7: Dow 2.0E3, log Dow 3.3
pH 11: Pow 2.4E4, log Pow 4.4
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.
