1,6-Naphthyridine-3-carboxamide, 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-1,4-dihydro-2,8-dimethyl-

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

GLP compliance:

no

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- pH of the blank buffer solution: checked at the beginning of the test
- pH of the hydrolysis solution: measured at each test point
- Temperature during the experiment: checked at each test point
- repeatability of the peak areas of the investigated components was checked by analyzing an independent control solution of the test item; peak areas of the three components investigated within this hydrolysis study were measured and compared
- suitability of the HPLC system during the hydrolysis study was verified on every day of application
- calibration was verified at each sampling date at the level of 4.94 mg/L by using a control calibration solution

Buffers:

- Buffer pH 4: Citric acid/NaOH/NaCl (Fluka, order no.: 33643)
- Buffer pH 7: KH2PO4/Na2HPO4 (Fluka, order no.: 33646)
- Buffer pH 9: Na2B4O7/HCl (Fluka, order no.: 33648)

Details on test conditions:

Preparation of a test item stock solution
- weighing of 22.3 mg of the test item in a 100 mL measuring flask which was then filled to the mark with acetonitrile, resulting in a final concentration of 223 mg/L

Preparation of the hydrolysis test solutions
- For each pH separate hydrolysis test solutions were prepared by dilution of 2 mL of the test item stock solution with 200 mL of the corresponding buffer systems. Test item concentrations of 9.0 mg/L were obtained.
- test item was applied as an aqueous solution (including 1 % acetonitrile) with a concentration of approx. 9 mg/L (water solubility estimated in a non-GLP pretest: 20 mg/L)
- Aliquots of the stock solutions were taken without further treatment to prepare individual vials for every test point
- Preparation was carried out under nitrogen as flushing gas
- vials were closed and incubated at 20 °C in a water bath under dark conditions
- at each test point the hydrolysis solution was directly led to the chromatographic measurement
- pH determination: pH-meter equipped with a calibrated single-rod glass electrode

Duration:

5 d

pH:

4

Temp.:

20 °C

Initial conc. measured:

8.952 mg/L

Duration:

5 d

pH:

7

Temp.:

20 °C

Initial conc. measured:

8.819 mg/L

Duration:

5 d

pH:

9

Temp.:

20 °C

Initial conc. measured:

8.726 mg/L

Transformation products:

no

% Recovery:

94.9

pH:

4

Temp.:

20 °C

Duration:

5 d

% Recovery:

96.7

pH:

7

Temp.:

20 °C

Duration:

5 d

% Recovery:

98.3

pH:

9

Temp.:

20 °C

Duration:

5 d

Details on results:

Rac-Amido-TH-naphthyridine is found to be stable at 20 °C at all three pH-values for 5 days. No half-life times and hydrolysis rates were calculated. Because no degradation was observed, no sterility test was performed in this case.

Validity criteria fulfilled:

yes

Conclusions:

Rac-Amido-TH-naphthyridin is found to be stable at 20 °C at all three pH-values for 5 days. No half-life times and hydrolysis rates were calculated.

Executive summary:

The test was performed based on OECD Guidelines for Testing of Chemicals, Section 1 – Physical-Chemical Properties, OECD TG 111, Council Regulation (EC) No 440/2008, Guideline Part C – Methods for the Determination of Ecotoxicity, C.7. “Abiotic Degradation: Hydrolysis as a Function of pH”.

The hydrolysis behaviour of Rac-Amido-TH-naphthyridin was investigated at 20 °C at pH 4, pH 7 and pH 9 over a period of five days according to OECD TG 111. The stability was monitored by HPLC analysis using UV-detection.

No abiotic degradation of the test item was observed. Rac-Amido-TH-naphthyridin is found to be stable at 20 °C at all three pH-values for 5 days. No half-life times and hydrolysis rates were calculated.

Description of key information

Rac-Amido-TH-naphthyridin is found to be stable at 20 °C at all three pH-values for 5 days. No half-life times and hydrolysis rates were calculated.