Cyclopenta[c]cyclopropa[g][1,6]diazacyclotetradecine-12a(1H)-carboxylic acid, 2,3,3a,4,5,6,7,8,9,11a,12,13,14,14a-tetradecahydro-2-[[7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]-4-quinolinyl]oxy]-5-methyl-4,14-dioxo-, ethyl ester, (2R,3aR,10Z,11aS,12aR,14aR)-

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 August - 04 December 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7840 (Water Solubility)

Deviations:

no

GLP compliance:

yes

Type of method:

column elution method

Test material

Test material information

Constituent 1

Reference substance name:

ethyl (1R,4R,6S,7Z,15R,17R)-17-({7-methoxy-8-methyl-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.0^{4,6}]octadec-7-ene-4-carboxylate

EC Number:

618-843-3

Cas Number:

923604-57-3

Molecular formula:

C37H46N4O6S

IUPAC Name:

ethyl (1R,4R,6S,7Z,15R,17R)-17-({7-methoxy-8-methyl-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.0^{4,6}]octadec-7-ene-4-carboxylate

Test material form:

solid

Details on test material:

- Name of test material (as cited in study reports): JNJ-38970191-AAA (T003009)
- Physical state: solid
- Appearance white solid

Specific details on test material used for the study:

- Batch n°: I15AB0148
- Analytical purity: 97.8%
- Expiration date: 21 January 2017
- Storage condition: at room temperature

Results and discussion

Water solubility

Key result

Water solubility:

ca. 1.44 µg/L

Conc. based on:

test mat. (dissolved fraction)

Temp.:

20 °C

pH:

>= 8.2 - <= 8.3

Details on results:

Preliminary test
The content of test item dissolved in the water sample was 0.05 µg/L after two centrifugation steps and 0.02 µg/L after three centrifugation steps.

Main test
The results for the samples taken at a flow rate of 12 and 24 mL/h are given in the table in the next section.
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. The turbidity of the eluates was < 0.2 NTU. According to this, no undissolved particles were detected in the eluates.
In a chromatogram of one of the blank samples, a peak was observed at the retention time of the test item. This was probably caused by carry-over since a similar response was observed in the analytical blank.

Any other information on results incl. tables

The results for the samples taken at a flow rate of 12 and 24 mL/h are given in the table below.

Flow rate (mL/h)	Mean (n=10) (µg/L)	CV (%)	Mean (µg/L)	Maximum Difference (MD) (%)	pH
24	1.48	4.5	1.44	5.0	8.3
12	1.41	9.3			8.2

Applicant's summary and conclusion

Conclusions:

The column elution method was applied for the determination of the water solubility of JNJ-38970191-AAA (T003009).
The water solubility of the test item at 20°C was 1.44 µg/L.
The pH of the aqueous samples was 8.2 – 8.3.