3-{2-[2-(3-azaniumylpropoxy)ethoxy]ethoxy}propan-1-aminium di[(2Z)-3-carboxyprop-2-enoate]

Additional physico-chemical information

Link to relevant study record(s)

Reference

Endpoint:

other: Removal of water (freeze drying)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9th May 2016 to 24th August 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

no guideline required

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Test item: 207396/A
- Identification: Bis-Aminopropyl Diglycol Dimaleate
- CAS Number: 1629579-82-3
- Appearance: Clear colourless to pale yellow liquid (determined by Charles River Den Bosch)
- Test item storage: At room temperature
- Purity/Composition: Not indicated
- Purity/composition correction factor: No correction factor required
- Test item handling: No specific handling conditions required
- Stability at higher temperatures: Yes, maximum temperature: 40°C, maximum duration: 60 minutes

Results

Calibration curve – AS1645

The calibration line was constructed excluding one data point, since the back calculated accuracy was > 15% from the nominal concentration Figure 1 (attached) illustrates the calibration curve and Table 1 shows the statistical parameters. There was a quadratic relationship between response and test item concentration in the range of 0.1 – 1 mg/L (in end solution). Since the coefficient of correlation (r) was > 0.99 and the back calculated accuracies of the remaining data points were in the range 85-115% the calibration line was accepted.

Table 1: Statistical parameters of the calibration curve – AS1645

Quadratic regression factor	-1.60 x 10^7
Linear regression factor	3.21 x 10^7
Intercept	-2.32 x 10^6
Weighting factor	1/concentration^2
r	0.996

Calibration curve – AS1646

The calibration line was constructed using all data points Figure 2 (attached) illustrates the calibration curve and Table 2 shows the statistical parameters. There was a linear relationship between response and AS1646 concentration in the range of 0.1 – 1 mg/L (in end solution). Since the coefficient of correlation (r) was > 0.99 and the back calculated accuracies of the data points were in the range 85-115% the calibration line was accepted.

Table 2: Statistical parameters of the calibration curve – AS1646

Slope	47.0 x 10^2
Intercept	-26.6
Weighting factor	1/concentration^2
r	0.998

Analysis of the test samples

Chromatograms of a AS1645 calibration solution, undried test item (207396/A) and dried test item (207396/B) are shown in Figure 3, Figure 4 and Figure 5, respectively (attached).

Chromatograms of a AS1646 calibration solution, undried test item (207396/A) and dried test item (207396/B) are shown in Figure 6, Figure 7 and Figure 8, respectively (attached).

Content of 4,7,10-trioxa-1,13-tridecanediamine and maleic acid for the undried test item (207396/A) and dried test item (207396/B) are given in Table 3 and Table 4 respectively.

Table 3: 4,7,10-trioxa-1,13-tridecanediamine content

	Sample weight [mg]		Amount [mg]	Content [g/kg]
	Not corrected for water content	Corrected for water content		Not corrected for water content	Corrected for water content
undried test item (207396/A)	138	35.8	16.6	120	463
dried test item (207396/B)	100	94.8	42.7	426	451

Table 4: Maleic acid content

	Sample weight [mg]		Amount [mg]	Content [g/kg]
	Not corrected for water content	Corrected for water content		Not corrected for water content	Corrected for water content
undried test item (207396/A)	106	27.6	13.7	129	494
dried test item (207396/B)	94.4	89.3	26.8	283	300

Conclusions:

The 4,7,10-trioxa-1,13-tridecanediamine and maleic acid contents of the undried test item (207396/A) and dried test item (207396/B) were determined by LC-MS. The results of the study samples after correction of the sample weights for the water content are as follows:
- Undried test item water content: 74 %, and
- Dried test item water content: 5.4 %.

Executive summary:

Bis-aminopropyl diglycol dimaleate was freeze dried in a study performed to recognised standards. The water content, 4,7,10-trioxa-1,13 -tridecanediamine content and maleic acid content were determined before and after the freeze drying process. The results are given in the table below:

		4,7,10-trioxa-1,13-tridecanediamine content [g/kg]		maleic acid content [g/kg]
	Water content (% w/w)	Not corrected for water content	Corrected for water content	Not corrected for water content	Corrected for water content
undried test item (207396/A)	74	120	463	129	494
dried test item (207396/B)	5.4	426	451	283	300

Description of key information

Summary

Bis-aminopropyl diglycol dimaleate was freeze dried. The water content, 4,7,10-trioxa-1,13 -tridecanediamine content and maleic acid content were determined before and after the freeze drying process. The results are given below.

	Water content [% w/w]	4,7,10-trioxa-1,13-tridecanediamine content [g/kg]		Maleic acid content [g/kg]
		Not corrected for water content	Corrected for water content	Not corrected for water content	Corrected for water content
undried test item (207396/A)	74	120	463	129	494
dried test item (207396/B)	5.4	426	451	283	300

Conclusion

The 4,7,10-trioxa-1,13-tridecanediamine and maleic acid contents of the undried test item (207396/A) and dried test item (207396/B) were determined by LC-MS(/MS). The results of the study samples after correction of the sample weights for the water content are:

 

	4,7,10-trioxa-1,13-tridecanediamine content [g/kg]		Maleic acid content [g/kg]
	Not corrected for water content	Corrected for water content	Not corrected for water content	Corrected for water content
undried test item (207396/A)	120	463	129	494
dried test item (207396/B)	426	451	283	300

 

Results

The table below shows the calibration results. The system was found to be accurate for the determination of the water content of the test item.

Date of analysis Water	Water standard (mg/g)	Certified water content (mg/g)	Analysed water content (mg/g)	Recovery (%)	Mean recovery (%)
25-May-16	0.1	0.1	0.104	104	105
	1	1	1	100	100
			1.01	101

 

The water content results of the undried and dried test item are given in the table below.

Date of analysis	Test item	Weight test item (g)	Analysed water (%)	Water content (%)	Mean water content (%)
25-May-16	undried	19.9	0.328	73.9	74
		39.5	0.69	73.4
25-May-16	dried	17.7	5.42	5.42	5.4
		24.5	5.43	5.43

 

Conclusion

The water contents of the undried test item (207396/A) and dried test item (207396/B) were determined by a Coulometric Karl Fischer titration.

Water contents of the undried and dried test item are:

Test item	Water content (% w/w)
Undried (207396/A)	74
Dried (207396/B)	5.4