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Partition coefficient

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Reference
Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
8 January 2018 to 16 February 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Version / remarks:
23 November 2004
Deviations:
no
Principles of method if other than guideline:
Principle of method validation

An ultra performance liquid chromatographic method with tandem mass spectrometric detection (UPLC-MS/MS) for the quantitative analysis of the test item in water was developed.
Research performed on method development included, but was not limited to, the selection of a solvent to dissolve the test item, a suitable detector and an appropriate combination of column (e.g. stationary phase, dimensions) and mobile phase. Optimizations were performed to obtain a specific method, enhance retention-time stability, limit carry-over and improve the peak shape within the selected calibration range.
Method development is archived in the raw data, only the conditions of the final validated analytical method are issued in the report. The conditions of the validated method were approved in the raw data.
Validation of the analytical method was performed for the following parameters:

Specificity
A test item solution and blank sample were analyzed by single injection. The analytical method was found to be specific if the blank chromatogram showed no response for the test item or a response of < 30% of the limit of quantification.

Calibration Curve
Calibration solutions were analyzed in duplicate. The response of the calibration solutions was correlated with concentration using regression analysis with a 1/concentration2 weighting factor. A calibration curve with a coefficient of correlation (r) of > 0.99 and back calculated accuracies of the calibration solutions in the range 85-115% was accepted.

Accuracy and Repeatability
Quality control (QC) samples were analyzed by single injection into the analytical system. The analytical method was considered applicable for the determination of the test item if the mean accuracy was in the range 70-110% and the coefficient of variation was ≤ 20%.

Limit of Quantification
The limit of quantification (LOQ) is defined as the lowest concentration level at which an accuracy in the range 70-110% and a repeatability of ≤ 20% is demonstrated. The LOQ was obtained from the data of the accuracy and repeatability test.

Stability of the Analytical System and End Solutions
Calibration solutions were injected throughout the validation sequence including the beginning and end. The analytical system and/or end solutions were found to be stable if the coefficient of variation on the responses of the solutions was ≤ 20%.

Stability of Stock Solutions
Stock solutions of the test item were stored at room temperature for at least 12 hours. Additional calibration solutions were prepared and analyzed by single injection. The stock solutions were found to be stable if the coefficient of variation on the response factors of the calibration solutions prepared with fresh and stored stock solutions was ≤ 10%.

Storage Stability of Samples
Additional QC samples were prepared and stored in the freezer (≤ -15°C) for at least 16 hours. On the day of analysis, the samples were thawed at room temperature and treated identically as freshly analyzed QC samples. The stored samples were found to be stable if the mean accuracy was in the range 70-110%.
GLP compliance:
yes (incl. certificate)
Type of method:
other: ultra performance liquid chromatographic (UPLC)
Partition coefficient type:
other: Mathanol-Water
Test material information:
Composition 1
Specific details on test material used for the study:
Identification: Dermol GTR
Appearance: Clear light amber liquid
Batch: P6096
Purity/Composition: >90%
Test item storage: At room temperature
Stable under storage conditions until: 15 October 2019 (expiry date)

Test Facility test item number: 209077/A
Purity/Composition correction factor: No correction factor required
Test item handling: No specific handling conditions required
Molecular structure: Not indicated
Molecular formula: C63H110O12
Molecular weight: 1059
Analytical method:
high-performance liquid chromatography
Key result
Type:
Pow
Partition coefficient:
> 16 000 000
Temp.:
35 °C
pH:
ca. 7
Key result
Type:
log Pow
Partition coefficient:
> 7.2
Temp.:
35 °C
pH:
ca. 7
Details on results:
See "Any other information" for results tables.

Calculation method

Pow Calculation

The Pow of the test item was calculated to be4.6´1020 (log Pow 20.7) using the Rekker calculation method.

pKa Values

No pKa values for acidic and basic groups in the molecular structure of the test item in the logarithm range of 1 - 14 were calculated.

1.1.2.              

UPLC-UV chromatograms of the test item solution and the corresponding blank are shown inFigure 4andFigure 5, respectively. In the chromatogram of the test item solution, four peaks with a retention time between 30.6 and 36.9 minutes were observed. The reference compounds are eluted in the isocratic part of the method, the retention time of 4,4’-DDT (log Pow = 6.5) andbenzo[ghi]perylene(log Pow = 7.2) were 12.0 and 18.8 minutes, respectively. It was concluded that the log Pow of test item was > 7.2 (Pow > 1.6 ´ 107).

See also attached chromatograms.

Conclusions:
The UPLC method at neutral pH was applied for the determination of the partition coefficient (Pow) of Dermol GTR. It was concluded that the log Pow of test item was > 7.2 (Pow > 1.6 x 10^7).
Executive summary:

In this guideline (OECD 117) study, conducted with GLP certification, the octanol-water partition coefficient (log Pow) of test item was > 7.2 (Pow > 1.6 x 10^7).

Description of key information

Study performed to recognised study guidelines with GLP certification.

Key value for chemical safety assessment

Additional information

In this guideline (OECD 117) study, conducted with GLP certification, the methanol-water partition coefficient (log Pow) of test item was > 7.2 (Pow > 1.6 x 10^7).