7-Cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb - Aug 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C)

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Calibration solutions were injected in duplicate. Test samples were analyzed by single injection.
The concentration of the test item in the test samples was determined immediately after preparation (t=0) and after 2.4 hours and 5 days. The samples taken at t=2.4 hours and t=5
days were cooled to room temperature using running tap water.
Analysis was performed on subsamples of 500 μL. The samples were diluted in a 1:1 (v:v) ratio with acetonitrile and analyzed.
Blank buffer solutions containing a similar content of blank spiking solution were treated similarly as the test samples and analyzed at t=0.
The pH of each of the test solutions (except for the blanks) was determined at each sampling time.

Buffers:

Acetate buffer pH 4, 0.1 M
Solution of 16.7% 0.1 M sodium acetate in water and 83.3% 0.1 M acetic acid in water. Buffer contained 0.0009% (w/v) sodium azide.
Phosphate buffer pH 7, 0.1 M
Solution of 0.1 M potassium di-hydrogenphosphate in water adjusted to pH 7 using 10 N sodium hydroxide. Buffer contained 0.0009% (w/v) sodium azide.
Borate buffer pH 9, 0.1 M
Solution of 0.1 M boric acid in water and 0.1 M potassium chloride in water adjusted to pH 9 using 10 N sodium hydroxide. Buffer contained 0.0009% (w/v) sodium azide.

Details on test conditions:

The buffer solutions were filter-sterilised through a 0.2 μm FP 30/0.2 CA-S filter (Whatman, Dassel, Germany) and transferred into a sterile vessel. To exclude oxygen, nitrogen gas was
purged through the solution for 5 minutes. The test item was spiked to the solutions at a target concentration of 10 mg/L using a spiking solution in 50/50 (v/v) acetonitrile/water. For each
sampling time, duplicate sterile vessels under vacuum were filled with 6 mL test solution and placed in the dark in a temperature controlled environment at 50.1°C ± 0.2°C.

Duration:

5 d

pH:

4

Temp.:

25 °C

Initial conc. measured:

>= 10.5 - <= 10.9 mg/L

Duration:

5 d

pH:

7

Temp.:

25 °C

Initial conc. measured:

>= 10.3 - <= 10.8 mg/L

Duration:

5 d

pH:

9

Temp.:

25 °C

Initial conc. measured:

>= 10.3 - <= 10.7 mg/L

Number of replicates:

2

Positive controls:

no

Negative controls:

no

Preliminary study:

At pH 4, pH 7 and pH 9, a degree of hydrolysis of < 10% was observed after 5 days. It demonstrated that the half-life time of the test item at 25°C is > 1 year.

Transformation products:

no

% Recovery:

< 10

St. dev.:

1

pH:

4

Temp.:

25 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

< 10

St. dev.:

1

pH:

7

Temp.:

25 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

% Recovery:

< 10

St. dev.:

1

pH:

9

Temp.:

25 °C

Duration:

5 d

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Type:

not specified

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Type:

not specified

Remarks on result:

hydrolytically stable based on preliminary test

Key result

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Type:

not specified

Remarks on result:

hydrolytically stable based on preliminary test

pH code	Nominal concentration [mg/L]	Analyzed concentration [mg/L]	Individual Recovery [%]	Mean Recovery [%]
pH 4	10.0 10.0	10.7 10.5	107 105	106
pH 7	10.0 10.0	10.8  10.8	108 108	108
pH 9	10.0 10.0	10.7  10.6	107 106	106

Validity criteria fulfilled:

yes

Conclusions:

Hydrolysis as a function of pH:
pH 4: t½ > 1 year
pH 7: t½ > 1 year
pH 9: t½ > 1 year

Description of key information

Hydrolysis as a function of pH:

pH 4: t½ > 1 year

pH 7: t½ > 1 year

pH 9: t½ > 1 year

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C