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Stability in organic solvents and identity of relevant degradation products

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Reference
Endpoint:
stability in organic solvents and identity of relevant degradation products
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 September 2015 to 18 December 2015
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.
Qualifier:
no guideline available
Principles of method if other than guideline:
GC method using FID for the determination of concentration and stability in formulations containing test item and peanut oil.
GLP compliance:
yes
Test substance stable:
yes
Transformation products:
not measured

- Under the described chromatographic conditions, the retention time of the test item was approximately 8.6 minutes.

- The total analysis time for each run was 10.0 minutes.

- Assay specificity/selectivity was confirmed when GC/FID analysis of processed vehicle samples revealed no significant peaks (with S/N > 10) at or near the retention time for the test item.

- The post-storage test item concentrations ranged from 94.3 % to 117 % of the pre-storage values.

- Formulations prepared at target concentrations of 20 to 220 mg/mL test item met the protocol requirements for homogeneity, resuspension homogeneity and stability.
Conclusions:
Formulations prepared in peanut oil at target concentrations of 20.0 and 220 mg/mL met the protocol-specified acceptance criteria for homogeneity and for resuspension homogeneity and stability after storage at room temperature for 5 and 11 days.
Executive summary:

METHOD

Test item concentration from 20.0 to 220 mg/mL in peanut oil was determined using a GC method and FID. Test item stability was assessed in calibration standards and processed QC samples stored at room temperature for 1 day. Test substance homogeneity and, following 5 and 11 days of room temperature storage, resuspension homogeneity and stability were assessed in the formulations containing target concentrations of 20 and 22 mg/mL test item.

 

RESULTS

The test material assay procedure was validated in this study with three validation sessions. Quantitation was performed using calibration standards ranging in test item concentration from 750 to 1000 µg/mL. The mean back-calculated standard concentrations had inter-session variability ranging from 0.94 % to 2.8 % Relative Standard Deviation (RSD) and % RE (% Relative Error) ranging from -0.45 % to 0.47 %, which met the protocol-specified acceptance criteria for calibration standards i.e. RSD ≤ 10 % and %RE within ± 10 % (except at the lowest level where RSD ≤ 15 % and %RE ± 15 % were acceptable). Assay precision and accuracy were verified by the analysis of QC samples prepared at 20.0, 100 and 220 mg/mL test item. The mean calculated QC concentrations had inter-session variability (precision) ranging from 2.8 % to 4 % RSD and %RE (accuracy) ranging from -7.9 % to -2.2 %. The results met the protocol-specified acceptance criteria for precision and accuracy i.e RSD ≤ 15 % and %RE ± 15 %.

 

The test substance in calibration standards and processed QC samples stored at room temperature for 1 day met the protocol-specified acceptance criteria for stability i.e the post-storage concentration was not < 90 % of the pre-storage value.

 

The results of the test substance homogeneity assessment in formulations prepared at target concentrations of 20 and 200 mg/mL test item met the protocol-specified acceptance criteria i.e. the RSD for the mean concentration was ≤ 10 % at a concentration within the acceptable limits (85 % to 115 % of target). Assessment of test substance resuspension homogeneity and stability in formulations prepared at target concentrations of 20 and 220 mg/mL and, following 5 and 11 days of room temperature storage, met the protocol-specified acceptance criteria for resuspension homogeneity i.e. the RSD for the mean concentration was ≤ 10 % and the previously stated protocol-specified criteria for stability.

Description of key information

The post-storage test substance concentrations of formulations prepared at target test item concentrations of 20.0 and 220 mg/mL ranged from 94.3 % to 117 % of the pre-storage values.

Additional information

Formulations prepared in peanut oil at target concentrations of 20.0 and 220 mg/mL met the protocol-specified acceptance criteria for homogeneity and for resuspension homogeneity and stability after storage at room temperature for 5 and 11 days.