3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 24, 2012 to October 26, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study (OECD109) with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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

GLP compliance:

no

Type of method:

flask method

Test material

Test material information

Constituent 1

Reference substance name:

3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

EC Number:

213-485-0

EC Name:

3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Cas Number:

957-68-6

Molecular formula:

C10H12N2O5S

IUPAC Name:

(6R,7R)-3-[(acetyloxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Name: 7-Aminocefalosporansäure (7-ACA)
Lot no.: B146988

Results and discussion

Water solubility

Water solubility:

611 mg/L

Temp.:

20 °C

Any other information on results incl. tables

For the main test three flasks were prepared with an amount of test item and water, and one flask only with water. After stirring and centrifugation the aqueous phases were measured by means of HPLC. The solution of each flask has been measured twice. The results of these measurements are shown inTable4. The values represented in the table are rounded values. The calculation was carried out with the original not rounded values.

Table4: Results of the flask method

flask	1a	2a	3a	4a
measured value [mg/L]	6.16 / 6.11	6.30 / 6.28	5.91 / 5.90	0 / 0
aliquot of the flask [mL]	0.5	0.5	0.5	0.5
total volume after the 1^stdilution [mL]	25	25	25	25
aliquot of the 1^stdilution [mL]	1	1	1	1
total volume after the 2^nddilution [mL]	2	2	2	2
water solubility [mg/L]	615.8 / 610.5	629.9 / 627.6	590.6 / 589.6	0 / 0
average water solubility [mg/L]	613.2	628.7	590.1	0
mean value of the water solubility [mg/L]	610.7
standard deviation [mg/L]	19.4
relative standard deviation [%]	3.2

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): moderately soluble (100-1000 mg/L)
According to OECD Test Guideline 105 and EC No. 440/2008 Part A. Method A.6. the water solubility at 20 °C of test item 7-Aminocephalosporanic acid was determined to be:
cS = 611 mg/L
RSD = 3.2 %

Executive summary:

The quantity of test item necessary to saturate the desired volume of water was estimated from the preliminary test to be 1.01 g/L at most. About five times that quantity were weighed into each of three flasks fitted with glass stoppers (seeTable1). After addition of 100 ml of distilled water to each flask the flasks were stirred at 30 °C for different periods of time (24, 48 and 72 h).

After stirring at 30 °C the flasks were cooled down to 20 °C and stirred at 20 °C for further 24 h. After 24 h stirring time the contents of the flasks were centrifuged for 30 min at 20 °C with 15000 rpm.

For the analytical measurement by means of HPLC the centrifuged clear aqueous phases were diluted from 0.5 ml to 25 ml and again 1:1 with the eluent.

One additional flask was prepared as blank measurement. Therefore distilled water was added to the flask, stirred for 72 h at 30 °C and treated like the other samples.

The masses and stirring times for the four flasks are shown inTable1.

Table1: Flask method for the determination of the water solubility

flask	1a	2a	3a	4a
mass [g]	5.03	5.04	5.04	--
stirring time at 30°C [h]	72	48	24	72
stirring time at 20°C [h]	24	24	24	24
pH value	3.8	3.7	3.8	6.5