4-[bis(phenylsubstituted)substituted]phthalic acid

Dissociation constant

Administrative data

Endpoint:

dissociation constant

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study initiation date: July 8, 2015: Study completion date: December 1, 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 112 (Dissociation Constants in Water)

GLP compliance:

not specified

Test material

Reference

Name:

Unnamed

Type:

Constituent

Type:

impurity

Test material form:

solid: particulate/powder

Results and discussion

Dissociating properties:

yes

Dissociation constant

Temp.:

40 °C

Remarks on result:

other: As determined by HPLC, it was concluded that the test item has undissociated form less than pH 1.2

Any other information on results incl. tables

Confirmation of solution stability of test item results and discussion

The change of the spectrum was not confirmed in acid solution. The change of the spectrum was confirmed in the buffer solution (pH 4.2) and alkaline solution. Therefore, the spectrometric method was not able to apply because the test item was changed in the pH range where dissociation of the test item was expected.

Evaluation of dissociated/undissociated form by HPLC results and discussion

The retention times of the test item are shown in the table below. The peaks of the test item were not detected in the eluent (more than pH 5.0) and the peaks of converted products were detected. Therefore, it was difficult to evaluate the dissociated/undissociated form of the test item at more than pH 5.0.

In view of the reverse phase HPLC analysis for dissociative substances, it is well known that the retention time become the maximum and constant at undissociated form. In this study, the retention times of the test item were approximately constant less than pH 1.2. Therefore, it was considered that the test item has undissociated form in less than pH 1.2.

pH of buffer solution		Retention time (min)			Remarks
		Measurement value		Average
1.0	Main component	10.46	10.50	10.48	-
	Sub component	29.96	30.01	29.99
1.2	Main component	10.30	10.32	10.31	-
	Sub component	29.79	29.81	29.80
2.0	Main component	9.50	9.53	9.52	-
	Sub component	28.83	28.83	28.83
4.0	Main component	6.33	6.33	6.33	-
	Sub component	19.00	19.00	19.00
5.0	Main component	-	-	-	Converted products were detected
	Sub component	-	-	-
7.0	Main component	-	-	-	Converted products were detected
	Sub component	-	-	-
10.0	Main component	-	-	-	Converted products were detected
	Sub component	-	-	-
12.0	Main component	-	-	-	Converted products were detected
	Sub component	-	-	-

Applicant's summary and conclusion

Conclusions:

The dissociation constant was not able to measured by the spectrometric method because the test item was changed in the pH range where dissociation of the test item was expected. Therefore, the dissociated/undissociated form of the test item was evaluated using HPLC and it is concluded that the test item has undissociated form less than pH 1.2.

Executive summary:

Test item: CIM-43

Objective: This study was performed to evaluate the dissociated/undissociated form of CIM-43

Test method: OECD guidelines for testing of chemical No.112, May 12, 1981, “Dissociation constants in water: Spectrometric Method”

The spectrometric method was not able to apply because the test item was converted in the test solution. Therefore, the dissociated/undissociated form of the test item was evaluated by high-performance liquid chromatography (HPLC).

Results: The dissociation constant was not able to measure by the spectrometric method because the test item was changed in the pH range where dissociation of the test item was expected. Therefore, the dissociated/undissociated form of the test item was evaluated using HPLC and it is concluded that the test item has undissociated form less than pH 1.2.