[2S-[2α,5α,6β(S*)]]-6-[[[[(4-ethyl-2,3-dioxopiperazin-1-yl)carbonyl]amino]phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05/09/2018 - 17/09/2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Key result

Water solubility:

0.257 g/L

Conc. based on:

test mat.

Incubation duration:

72 h

Temp.:

20 °C

pH:

>= 3.41 - <= 3.42

Table 1. Results of test item solubility in water

Mixing time at 30 ºC [days, flasks]	1		2		3
Samples	1	2	3	4	5	6
Temperature, ºC	19.7		20.1		19.8
pH	3.42		3.41		3.41
Concentration of Piperacillin acid, g/kg	0.2563	0.2567	0.2558	0.2579	0.2561	0.2581
Average concentration of Piperacillin acid, g/kg	0.2565		0.2569		0.2571
Average concentration Piperacillin acid, g/kg	0.2568

Table 2. Results of preliminary test

0.1g in x mL of solution	0.1	0.5	1	2	10	100	> 100
Soluble (+/-)	-	-	-	-	-	-	+
Approximate solubility, g/L	> 1000	1000 to 200	200 to 100	100 to 50	50 to 10	10 to 1	< 1

Table 3. Calibration solution

Day	Weight [mg]	Dilution [mL]	Cw [mg/mL]	Peak area		Average peak area Aw	f	Average f
1	20.50	25-0.1-25	0.0032636	36942	38229	37585.5	0.00008683	0.00008737
		25-0.2-25	0.0065272	74595	73908	74251.5	0.00008791
2	20.50	25-0.2-10	0.016318	209840	210782	210311	0.00007992	0.00008188
		25-0.4-10	0.0327952	398554	407133	402843.5	0.00008385
3	20.50	25-0.2-10	0.016318	205272	205277	205274.5	0.00007949	0.00008038
		25-0.4-10	0.032636	403576	399659	401617.5	0.00008126

Table 4. Study solution

Sample day/ flask		Weight of the sample [mg]	Dilution [mL]	Cp [mg/mL]	Peak area		Average peak area Ap	X [g/kg]
1	1	2018.30	5-0.2-10	8.0732	23947	23413	23680.0	0.2563
	2	2020.00		8.0800	23605	23882	23743.5	0.2567
2	3	2012.20	5-1-10	40.2440	125716	125754	125735.0	0.2558
	4	2020.25		40.4050	126569	127911	127240.0	0.2579
3	5	1996.35	5-1-10	39.9270	117181	116856	117018.5	0.2561
	6	2010.90		40.2180	119177	118464	118820.5	0.2581

Conclusions:

The water solubility of the test item at 20ºC is 0.2568 g/L.

Executive summary:

The water solubility of the test item was determined using the shake flask method and following OECD TG 105 and EU A.6 method, under GLP conditions. Based on a preliminary test, three 100 ml beakers were filled with 5 times this concentration. The flasks were centrifuged for one day at 20ºC, and two and three days at 30ºC, respectively. The concentration of the test substance was measured with a validated HPLC method and since results of the three vessels did not differ by more than 15% the test was considered satisfactory. Two replicate measurements were performed. The water solubility of the test item was 0.2568 g/L at 20 ± 0.5 °C (pH 3.41-3.42).

Description of key information

Key study. Method according to OECD 105/ EU A.6, GLP study. The water solubility of the test item at 20ºC is 0.2568 g/l.

Key value for chemical safety assessment

Water solubility:

0.257 g/L

at the temperature of:

20 °C

Additional information

Water solubility of the test item was determined using the shake flask method and following OECD guideline 105 and EU method A.8, under GLP conditions. After a preliminary test to determine the necessary concentration to saturate 70 mL of water, three 100 ml beakers were filled with 5 times this concentration. The three flasks were centrifuged for one day at 20ºC, and two and three days at 30ºC respectively. The concentration of the test substance was measured with a validated HPLC method and since results of the three vessels did not differ by more than 15% the test was considered satisfactory. Two replicate measurements were performed. The water solubility of the test item was 0.2568 g/l at 20 ± 0.5 °C (pH 3.41-3.42).