tert-butyl {(1S)-2-[(1S,3S,5S)-3-cyano-2-azabicyclo[3.1.0]hex-2-yl]-1-[3-hydroxyadamantan-1-yl]-2-oxoethyl}carbamate

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 07 February and 15 March 2012.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

using the flask method, designed to be compatible with Method A6 Water Solubility of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 105 of the OECD Guidelines for Testing of Chemicals, 27 July 1995.

Deviations:

no

GLP compliance:

yes

Type of method:

flask method

Remarks:

Using the flask method, designed to be compatible with Method A6 Water Solubility of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 105 of the OECD Guidelines for Testing of Chemicals, 27 July 1995.

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

Identification: BMS-528235-01
Description: Off white powder
Batch: 1L63487N
Purity: 98.6 %
Expiry Date: 27 November 2014
Storage Conditions: Room temperature in the dark

Results and discussion

Water solubility

Water solubility:

0.864 g/L

Temp.:

20 °C

Remarks on result:

other: pH not reported

Details on results:

Due to the tabular nature of this information & to retain the integrity & coherence of the original Harlan Laboratories Ltd. Study report please see section “Any other information on results incl. tables”

Any other information on results incl. tables

Results

Preliminary test

The preliminary estimate of water solubility was 0.874 g/L at 20 °C

Please see Attachment 1 for Typical Chromatography.

The mean peak areas relating to the standard and sample solutions are shown in the following table:

 

Table 3.11

 

Solution	Mean Peak Area
Standard 101 mg/L	2.8865 x 10^7
Standard 107 mg/L	3.0524 x 10^7
Sample 1A	2.4462 x 10^7
Sample 1B	2.4452 x 10^7
Sample 2A	2.4709 x 10^7
Sample 2B	2.4737 x 10^7
Sample 3A	2.4896 x 10^7
Sample 3B	2.4866 x 10^7

 

 

The concentration (g/L) of test item in the sample solutions is shown in the following table:

 

Table 3.12

 

Sample Number	Time Shaken at ~ 30 ºC (hours)	Time Equilibrated at 20 ºC (hours)	Concentration (g/L)	Solution pH
1	72	24	0.856	6.9
2	48	24	0.865	6.8
3	24	24	0.871	6.9

 

Mean concentration:  0.864 g/L at 20.0 ± 0.5 ºC
Range:                        0.856 to 0.871 g/L

 

Validation

The linearity of the detector response with respect to concentration was assessed over the concentration range of 10.1 to 201 mg/L. This was satisfactory with a correlation coefficient (r²) of 1.000 being obtained.

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): moderately soluble (100-1000 mg/L)
The water solubility of the test item has been determined to be 0.864 g/L of solution at 20.0 ± 0.5 °C.

Executive summary:

The determination was carried out using the flask method designed to be compatible with Method A6 Water Solubility of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 105 of the OECD Guidelines for Testing of Chemicals, 27 July 1995. Conclusion The water solubility of the test item has been determined to be 0.864 g/L of solution at 20.0 ± 0.5 °C.