cyproconazole (ISO); (2RS,3RS;2RS,3SR)-2-(4-chlorophenyl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 Dec 1998 to 30 Dec 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: CIPAC MT157.1

GLP compliance:

yes

Type of method:

flask method

Key result

Water solubility:

93 mg/L

Conc. based on:

test mat.

Loading of aqueous phase:

250 mg/L

Incubation duration:

72 h

Temp.:

22 °C

pH:

7.1

RESULTS

Six solutions containing known amounts of the cyproconazole reference substance and p-chlorobenzophenone as internal standard were used as calibration solutions. These solutions and the diluted test solutions, were injected into the HPLC. The peak areas were integrated and the content of the individual diastereomers A and B in the sample solutions were calculated as mg in 10 mL test solution (see Table 1 in “Any other information on results incl. tables”).

The sum of the diastereomers A and B gives the concentration of test substance, calculated as mg of the 100 % pure material in 10 mL test solution. Based on these figures, the solubility of test substance and the individual diastereomers were calculated in ppm or mg/1000 mL aqueous solution.

 

SOLUBILITY

Solubility at pH 4.1

Test substance:           108 ± 8 ppm

diastereomer A            51 ± 3 ppm

diastereomer B:           57 ± 6 ppm

 

Solubility at pH 7.1

Test substance:           93 ± 18 ppm

diastereomer A            46 ± 9 ppm

diastereomer B:           47 ± 9 ppm

 

 

Solubility at pH 10

Test substance:           109 ± 4 ppm

diastereomer A            54 ± 2 ppm

diastereomer B:           55 ± 3 ppm

INTERPRETATION

The calibration curve which was obtained from the calibration solutions at the various concentration levels was found to be very accurate, the relative standard deviation being less than 1 %. The results calculated for the samples exhibit somewhat bigger deviations. The range of the relative standard deviations is between 4 and 10 % in the sample solutions at pH 4 and 10, but about 20 % in the solutions at pH 7. However, no significant trend in increased water solubility could be observed during prolonged equilibration periods. This indicates that the equilibrium plateau was reached even after short investigation period and that substance was not degraded during the whole experiment. The ratio of the diastereomers A to B is about 49 : 51 in the solid test material, whereas the ratio in the saturated aqueous solutions is found to be in the range of 47 : 53 at pH 4, 49 : 51 at pH 7 and 50 : 50 at pH 10. Therefore, no preference of one of the diastereomer over the other could be observed during the solubility step.

Table 1: Analytical results

Sample No.	Time in hours at		pH	mg substance/10 mL tests solution
	30 °C	22.0 °C		diaster A	diaster B	a.i.
Buffer solution pH 4.0
4/24/1	24	65	4.1	0.51	0.63	1.14
4/24/2				0.50	0.62	1.12
4/48/1	48	65	4.1	0.45	0.47	0.92
4/48/2				0.54	0.56	1.10
4/72/1	72	65	4.1	0.54	0.59	1.13
4/72/2				0.52	0.58	1.1 0
Average				0.51 ± 0.03	0.57 ± 0.06	1.08 ± 0.08
Buffer solution pH 7.0
7/24/1	24	65	7.1	0.31	0.33	0.64
7/24/2				0.49	0.51	1.00
7/48/1	48	65	7.1	0.54	0.53	1.07
7/48/2				0.51	0.50	1.01
7/72/1	72	65	7.1	0.54	0.54	1 08
7/72/2				0.39	0.39	0!;.78
Average				0.46 ± 0.09	0.47 ± 0.09	0.93 ± 0.18
Buffer solution pH 10.0
10/24/1	24	65	10	0.53	0.55	1.08
10/24/2				0.51	0.52	1.03
10/48/1	48	65	9.9	0.53	0.53	1.06
10/48/2				0.56	0.55	1.11
10/72/1	72	65	10	0.54	0.58	1.1 2
10/72/2				0.55	0.59	1.14
Average				0.54 ± 0.02	0.55 ± 0.03	1.09 ± 0.04

Conclusions:

The water solubility of pure test substance at 22 °C is 108 ± 8 mg/L at pH 4.1, 93 ± 18 mg/L at pH 7.1 and, 109 ± 4 mg/L at pH 10.0.

Executive summary:

The water solubility of the pure test substance has been determined using the flask method in accordance with CIPAC MT157.1 and in compliance with GLP criteria. At 22 °C the water solubility was 108 ± 8 mg/L at pH 4.1, 93 ± 18 mg/L at pH 7.1 and, 109 ± 4 mg/L at pH 10.0.

Description of key information

93 mg/L in water at 22 °C at pH 7.1, flask method, CIPAC MT157.1, Wisson 19897.

Key value for chemical safety assessment

Water solubility:

93 mg/L

at the temperature of:

22 °C