4-chloro-N-[2-methoxy-4-(morpholin-4-yl)-5-nitrophenyl]pyrimidin-2-amine

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-03-30 to 2021-05-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

2016

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

1995

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

column elution method

Test material

Test material information

Constituent 1

Reference substance name:

4-chloro-N-[2-methoxy-4-(morpholin-4-yl)-5-nitrophenyl]pyrimidin-2-amine

Cas Number:

2270944-70-0

Molecular formula:

C15H16ClN5O4

IUPAC Name:

4-chloro-N-[2-methoxy-4-(morpholin-4-yl)-5-nitrophenyl]pyrimidin-2-amine

Test material form:

solid: particulate/powder

Results and discussion

Water solubility

Key result

Water solubility:

0.425 mg/L

Conc. based on:

test mat.

Remarks:

The water solubility of a test item is specified by the saturation mass concentration of the test item in water at a given temperature and is expressed in g/L or equivalent.

Temp.:

20 °C

pH:

>= 7.5 - <= 7.8

Remarks on result:

other: The pH of the aqueous samples was 7.8 and 7.5.

Details on results:

Preliminary Test:
The content of test item dissolved in the water sample was 0.662 mg/L.
Main Study:
The turbity of a blank and a sampled fraction at both flow rates was measured. A turbity below 0.2 NTU indicates that no undissolved material is present. The NTU values above 0.2 NTU for the sample fractions from the column with carrier loaded with test item, indicate undissolved material. However, since the corresponding blank fraction demonstrated NTU values between 0.1 and 0.2 and since the increase in turbity was < 0.2 NTU, the increase was considered as acceptable and it was decided to continue the water solubility main study.

The coefficient of variation (CV) (n = 10) was ≤ 30% at both flow rates. It demonstrated that the system was equilibrated at all flow rates.
The maximum difference (MD) on the mean values of the samples at both flow rates was also ≤ 30%. Based on this, the water solubility of the test item is given as the mean value of these measurements.
Small responses at the retention time of the test item were detected in the chromatograms of the pretreated samples from the blank column. The maximum contribution to the samples was 0.96%. It was considered that it has no significant effect on the results of the test samples.

Any other information on results incl. tables

Main study - water solubility of the test item

Flow rate mL/h	Sample no.	Concentration analyzed					pH
		Individual [mg/L]	Mean^1	CV [%]	Mean^2 [mg/L]	MD [%]
24	1 2 3 4 5 6 7 8 9 10	0.431 0.439 0.430 0.407 0.430 0.406 0.413 0.423 0.349 ^3 0.420	0.422	2.8	0.425	1.2	7.8
12	1 2 3 4 5 6 7 8 9 10	0.496 ^3,4 0.430 0.431 0.436 0.429 0.427 0.421 0.421 0.424	0.427	1.2			7.5

¹ Mean of the concentrations obtained at one flow rate.
² Mean of the concentrations obtained at both flow rates.
³ This value was not used for calculation of the mean because it is an outlier according to Dixon’s Q test
⁴ This value was not used for calculation of the mean because the system had not reached equilibrium yet.

Applicant's summary and conclusion

Conclusions:

The column elution method was applied for the determination of the water solubility of
JNJ-73848242-AAA (T003901).
The water solubility of the test item at 20°C was 0.425 mg/L.
The pH of the aqueous samples was 7.8 and 7.5.