1H-Pyrazolo[3,4-c]pyridine-3-carboxylic acid, 4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-, ethyl ester

Adsorption / desorption

Link to relevant study record(s)

Reference

Endpoint:

adsorption / desorption: screening

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 June 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method C.19 (Estimation of the Adsorption Coefficient (KOC) on Soil and Sewage Sludge Using High Performance Liquid Chromatography (HPLC))

Version / remarks:

2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 121 (Estimation of the Adsorption Coefficient (Koc) on Soil and on Sewage Sludge using High Performance Liquid Chromatography (HPLC))

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC estimation method

Media:

soil

Radiolabelling:

no

Details on study design: HPLC method:

PKA CALCULATION
- Perrin calculation method (pKalc 5.0, module in Pallas 3.0, CompuDrug International, USA)
- Calculated pKa values in the logarithm range of 1 - 14: none
- Based on the result, the mobile phase was not buffered.

HPLC CONDITIONS
- Instrument: Acquity UPLC system (Waters, USA)
- Detector: Acquity UPLC TUV (Waters)
- Column: Acquity UPLC HSS Cyano, 100 mm x 2.1 mm i.d., dp = 1.8 µm (Waters)
- Column temperature: 35°C ± 1°C
- Mobile phase: 55/45 (v/v) methanol/water
- Flow: 0.4 mL/min
- Injection volume: 5 μL
- UV detection: 210 nm

UNRETAINED SUBSTANCE
- Formamide; dissolved in 55/45 (v/v) methanol/water

REFERENCE SUBSTANCES
- Reference substances: see the table in the result section .
- Stock solutions of the reference substances at concentrations of approximately 1 g/L in methanol were used. The stock solutions were diluted to obtain an end solution of 55/45 (v/v) methanol/water.

TEST SUBSTANCE
A 1000 mg/L stock solution of the test item was prepared in methanol. In order to dissolve the test item the stock solution was ultrasonicated for 5 minutes. The stock solution was diluted to obtain an end solution of 55/45 (v/v) methanol/water. The final concentration of the test item solution was 10.0 mg/L.

PERFORMANCE OF THE TEST
- Solutions of the unretained substance, the reference substances and the test substance were injected in duplicate.
- Blank solution (55/45 (v/v) methanol/water) was analysed by single injection.

DATA HANDLING
- Dead time (t0) was calculated as the mean retention time of the unretained substance.
- Using the retention time (tr) the capacity factor (k') was calculated for each reference substance: k'= (tr-t0)/t0
- Log k’ values of the references substances were plotted against the known log Koc values.
- Linear regression analysis (least squares method) was used to calculate the regression line.
- Regression line: log k’ = 0.318 x log Koc – 0.778 (r= 0.98, n=16).
- Capacity factor (k') of the test substance was calculated from its mean retention time and the dead time.
- Log Koc of the test substance was calculated by substituting the log k’ in the regression line.
- The value of log Koc obtained from duplicate measurements was within ± 0.25 log unit.

Key result

Type:

log Koc

Value:

3.45 dimensionless

Temp.:

20 °C

Remarks on result:

other:

Remarks:

non-buffered mobile phase

Key result

Type:

Koc

Value:

2 800 dimensionless

Temp.:

20 °C

Details on results (HPLC method):

In the UPLC chromatogram of the 10 mg/L test substance solution, one test substance peak was observed.

Table: Results estimation method

 

Substance	tr,1 [min]	tr,2 [min]	mean tr (n=2)	log Koc	Koc
Formamide (t0)	0.760	0.798	0.779
Acetanilide	1.047	1.076		1.26
Monuron	1.295	1.335		1.99
2,5-Dichloroaniline	1.495	1.535		2.55
Naphthalene	1.737	1.791		2.75
Benzoic acid phenylester	2.056	2.108		2.87
Fenthion	2.791	2.871		3.31
Phenanthrene	3.089	3.164		4.09
4,4’-DDT	7.759	8.005		5.63
Test item	2.442	2.359	2.401	3.45	2.8E03

 

Remark: the log Koc values of the reference substances are mentioned in OECD TG 121 and are based on soil adsorption data.

Validity criteria fulfilled:

yes

Conclusions:

Using the HPLC estimation method using soil-adsorption-reference data, the log Koc for BMS-589154-01 was determined to be 3.45 (Koc= 2.8E03).

Executive summary:

The HPLC estimation method based on soil-adsorption reference data was used for the determination of the adsorption coefficient (Koc) of BMS-589154-01. The mobile phase was 55/45 (v/v) methanol/water. The stationary phase contained cyanopropyl chains chemically bonded to silica. The study was performed in accordance with EC C.9 and OECD 121 and in compliance with GLP.

 

The HPLC chromatogram of a 10 mg/L BMS-589154-01 solution showed one test substance peak. The log Koc value for the test substance at neutral pH has been determined as 3.45 (Koc= 2.8E03).

Description of key information

Using the HPLC estimation method using soil-adsorption-reference data, the log Koc for BMS-589154-01 was determined to be 3.45 (Koc= 2.8E03).

Key value for chemical safety assessment

Koc at 20 °C:

2 800