Disodium-3,3´-{Oxybis[2,1-ethanediyloxy(1-oxo-2,1-ethanediyl)imino]}bis(2,4,6-triiodobenzoate)

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method A.8 (Partition Coefficient - Shake Flask Method)

Deviations:

no

GLP compliance:

not specified

Type of method:

flask method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 61703003

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

> 2.86 - < 2.9

Temp.:

25 °C

pH:

ca. 1

Key result

Type:

log Pow

Partition coefficient:

> -1.87 - < -1.83

Temp.:

25 °C

pH:

ca. 4

Key result

Type:

log Pow

Partition coefficient:

< 13

Temp.:

25 °C

pH:

ca. 7

Key result

Type:

log Pow

Partition coefficient:

< -3

Temp.:

25 °C

pH:

ca. 9

Details on results:

The partition coefficient of the test substance was calculated from the ratio of the concentrations found in the two phases at three different phase volume ratios n-octanol/aqueous buffer solution. In order to obtain a material balance, the sum of the test item concentrations in the octanolic and the aqueous phases after equilibration was compared with the test item concentrations in the stock solutions (octanolic at pH 1; aqueous at pH 4, 7 and 9).

Single values of the measurements at pH 1

 

cs	454.1 mg/l = 3.60 · 10-4 M
	Phase volume ratio n-octanol/water 2:1		Phase volume ratio n-octanol/water 1:1		Phase volume ratio n-octanol/water 1:2
	Sample 1	Sample 2	Sample 1	Sample 2	Sample 1	Sample 2
fo	5	5	5	5	5	5
Vo	10	10	10	10	10	10
co	455.8	460.2	452.2	462.8	462.1	460.4
fw	1	1	1	1	1	1
Vw	100	100	100	100	100	100
cw	0.644	0.575	0.582	0.59	0.608	0.611
Pow	708	800	777	784	760	754
log Pow	2.85	2.9	2.89	2.89	2.88	2.88
% re- covery	100.4	101.4	99.7	102	102	101.7

* detection limit of the HPLC method under consideration of the dilution before analysis

cs : concentration of ZK 2218 in stock solution (pH 1 and 4: octanolic, pH 7 and 9:

aqueous [mg/l]

fo : dilution factor, octanolic phase, refers to dilution of octanolic phase before analysis

Vo : injection volume, octanolic phase [μl]

co : equilibrium concentration of the test item in octanolic phase [mg/l]

fw : dilution factor, aqueous phase, refers to dilution of aqueous phase before analysis

cw : equilibrium concentration of the test item in aqueous phase [mg/l]

Pow = co/ cw : n-octanol/water partition coefficient

% recovery = ((co · Vwt + co ·Vot )/ cs · Vs ) · 100

% recovery : sum of amount in octanolic and aqueous phase after partitioning compared to applied

amount of the test item [%]

Vwt : total volume of aqueous phase [ml]

Vot : total volume of octanolic phase [ml]

Vs : volume of stock solution applied [ml]

 

 

Single values of the measurements at pH 4

 

cs	1184 mg/l = 9.40 · 10-4 M
	Phase volume ratio n-octanol/water 2:1		Phase volume ratio n-octanol/water 1:1		Phase volume ratio n-octanol/water 1:2
	Sample 1	Sample 2	Sample 1	Sample 2	Sample 1	Sample 2
fo	5	5	5	5	5	5
Vo	10	10	10	10	10	10
co	16.29	16.3	18.01	16.16	16.66	15.89
fw	10	10	10	10	10	10
Vw	25	25	25	25	25	25
cw	1173	1152	1171	1166	1172	1170
Pow	0.014	0.014	0.015	0.014	0.014	0.014
log Pow	-1.86	-1.85	-1.81	-1.86	-1.85	-1.87
% re- covery	101.8	100.1	100.4	99.8	99.7	99.5

 

Single values of the measurements at pH 7

 

cs	1188 mg/l = 9.43 · 10-4 M
	Phase volume ratio n-octanol/water 2:1		Phase volume ratio n-octanol/water 1:1		Phase volume ratio n-octanol/water 1:2
	Sample 1	Sample 2	Sample 1	Sample 2	Sample 1	Sample 2
fo	5	5	5	5	5	5
Vo	25	25	25	25	25	25
co	< 1.15*	< 1.15*	< 1.15*	< 1.15*	< 1.15*	< 1.15*
fw	10	10	10	10	10	10
Vw	25	25	25	25	25	25
cw	1172	1169	1183	1169	1175	1161
Pow	< 9.81 · 10-4	< 9.84 · 10-4	< 9.72 · 10-4	< 9.84 · 10-4	< 9.79 · 10-4	< 9.91 · 10-4
log Pow	< - 3.0	< - 3.0	< - 3.0	< - 3.0	< - 3.0	< - 3.0
% re- covery	98.8	98.6	99.7	98.5	99	97.8

 

 

Single values of the measurements at pH 9

 

cs	1200 mg/l = 9.53 · 10-4 M
	Phase volume ratio n-octanol/water 2:1		Phase volume ratio n-octanol/water 1:1		Phase volume ratio n-octanol/water 1:2
	Sample 1	Sample 2	Sample 1	Sample 2	Sample 1	Sample 2
fo	5	5	5	5	5	5
Vo	25	25	25	25	25	25
co	< 1.15*	< 1.15*	< 1.15*	< 1.15*	< 1.15*	< 1.15*
fw	10	10	10	10	10	10
Vw	25	25	25	25	25	25
cw	1187	1187	1185	1175	1180	1185
Pow	< 9.69 · 10-4	< 9.69 · 10-4	< 9.70 · 10-4	< 9.79 · 10-4	< 9.75 · 10-4	< 9.70 · 10-4
log Pow	< - 3.0	< - 3.0	< - 3.0	< - 3.0	< - 3.0	< - 3.0
% re- covery	99	99	98.8	97.9	98.4	98.8

 

From the ratio of the concentration of the test substance in the two phases (6 measurements at each pH value) the following mean partition coefficients were obtained for pH 1 and 4. The mean log Pow values together with their 95 % confidence intervals were calculated from the mean Pow values and their standard deviations.

 

The 95 % confidence intervals were calculated according to the formula:

95 % CI = ((tn-1)x s))/(n^1/2)

 

tn-1:integral limits of the t-distribution for (n-1) degrees of freedom and P = 95 % (n = 6 => tn-1 = 2.57)

s:     standard deviation

n:       degrees of freedom (= number of measurements, n = 6)

 

At pH 7 and 9, the concentration in the octanolic phases after partitioning was below the quantitation limit (L0O) of the HPLC method under consideration of the injection volume and dilution before analysis. Therefore the Pow and the log Pow values are only given as "smaller than - 3.0" and no confidence intervals were calculated.

 

Conclusions:

The flask-shaking method according to EU Testing Guideline A.8 was used to determine the partition coefficient of the test item at 25 °C. The test item was partitioned between n-octanol and aqueous buffer solutions. The test item concentration in each phase after equilibration was determined by HP
LC. The 95% confidence intervals for log Pow are as follows:

log Pow: 2.86 to 2.90 at pH 1
log Pow: - 1.87 to (- 1.83) at pH 4
log Pow: < - 3.0 at pH 7
log Pow: < - 3.0 at pH 9

Executive summary:

The flask-shaking method similar to EU Testing Guideline A.8 was used to determine the partition coefficient of the test item at 25 °C. The test item was partitioned between n-octanol and aqueous buffer solutions. The test item concentration in each phase after equilibration was determined by HPLC. The 95% confidence intervals for log Pow are as follows:

 

log Pow: 2.86 to 2.90 at pH 1

log Pow: - 1.87 to (- 1.83) at pH 4

log Pow: < - 3.0 at pH 7

log Pow: < - 3.0 at pH 9

Description of key information

The flask-shaking method according to EU Testing Guideline A.8 was used to determine the partition coefficient of the test item at 25 °C. The test item was partitioned between n-octanol and aqueous buffer solutions. The test item concentration in each phase after equilibration was determined by HP LC. The 95% confidence intervals for log Pow are as follows:

log Pow: 2.86 to 2.90 at pH 1

log Pow: - 1.87 to (- 1.83) at pH 4

log Pow: < - 3.0 at pH 7

log Pow: < - 3.0 at pH 9