Benzoyl chloride, 3-[[[2,3-bis(acetyloxy)propyl]amino]carbonyl]-2,4,6-triiodo-5-[(2-methoxyacetyl)amino]-

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

3 - 5 Jun 2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The rate of hydrolysis of ZK 91445 was to be determined at pH 4, 7 and 9.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

rac-3-(2,3-Diacetoxypropylcarbamoyl)-2,4,6-triiodo-5-methoxyacetylaminobenzoyl chloride

EC Number:

604-759-4

Cas Number:

150928-21-5

Molecular formula:

C18 H18 Cl I3 N2 O8

IUPAC Name:

rac-3-(2,3-Diacetoxypropylcarbamoyl)-2,4,6-triiodo-5-methoxyacetylaminobenzoyl chloride

Study design

Analytical monitoring:

yes

Details on sampling:

- Sampling: 0, 3, 16, 28 h

Buffers:

- pH: 4,7,9
- Type and final molarity of buffer: 0.05 M acetate buffer solution pH 4
0.05 M phosphate buffer solution pH 7
0.05 M borate buffer solution pH 9

Number of replicates:

Two replicates

Results and discussion

Transformation products:

yes

Identity of transformation products

No.:

#1

Reference

Reference substance name:

Unnamed

IUPAC name:

rac-5-Amino-N-(2,3-diacetoxypropyl)-2,4,6-triiodoisophthalamic acid

Inventory number:

InventoryMultipleMappingImpl [inventoryEntryValue=EC 602-891-7]

CAS number:

122731-59-3

Molecular formula:

C15 H15 I3 N2 O7

Molecular weight:

715.99

SMILES notation:

CC(=O)OCC(CNC(=O)C1=C(C(=C(C(=C1I)N)I)C(=O)O)I)OC(=O)C

InChl:

InChI=1S/C15H15I3N2O7/c1-5(21)26-4-7(27-6(2)22)3-20-14(23)8-10(16)9(15(24)25)12(18)13(19)11(8)17/h7H,3-4,19H2,1-2H3,(H,20,23)(H,24,25)

Details on hydrolysis and appearance of transformation product(s):

-ZK 91445 is hydrolyzed immediately after prepraration of the test solutions at pH 4, 7 and 9.Degradation of the acid chloride leads to the free acid ZK 96368 as primary hydrolysis product. After degradation to ZK 96368 subsequent, albeit much slower, cleavage of the two ester functions will occur at pH values ≥ 7 leading to ZK 37493 as final hydrolysis product. A hydrolysis study with ZK 91248 which is structurally similar to ZK 96368 gave the following half-lives at 25 °C: pH 4: stable, pH 7: 144 days, pH 9: 52 h.

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

Key result

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

> 13.9 h-1

DT50:

< 3 min

Type:

(pseudo-)first order (= half-life)

Dissipation DT50 of parent compound 2

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

> 13.9 h-1

DT50:

< 3 min

Type:

(pseudo-)first order (= half-life)

Dissipation DT50 of parent compound 3

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

> 13.9 h-1

DT50:

< 3 min

Type:

(pseudo-)first order (= half-life)

Applicant's summary and conclusion

Validity criteria fulfilled:

not applicable

Conclusions:

DT50 < 3 min for pH 4, 7 and 9.

Executive summary:

ZK 91445 is hydrolyzed immediately after preparation of the test solutions at pH 4, 7 and 9. Degradation of the acid chloride leads to the free acid ZK 96368 as primary hydrolysis product. After degradation to ZK 96368 subsequent, albeit much slower, cleavage of the two ester functions will occur at pH values ≥ 7 leading to ZK 37493 as final hydrolysis product. A hydrolysis study with ZK 91248 which is structurally similar to ZK 96368 gave the following half-lives at 25 °C: pH 4: stable, pH 7: 144 days, pH 9: 52 h.