The Atropomer Composition of Iopromide as an Indicator for Assessment of the Quality of its Substance and Medincal Formulations

• Published in: Pharmaceutical chemistry journal Vol. 48; no. 3; pp. 186 - 195
• Main Authors: Glushkov, R. G., Goizman, M. S., Arantseva, D. A., Demidova, N. N., Kulaeva, E. K., Zagudailova, M. B., Dmitriev, D. E., Trifilenkov, A. S., Korlyukov, A. A., Arkhipov, D. E., Suponitskii, K. Yu, Shimanovskii, N. L., Zaitsev, S. A., Degterev, E. V.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.06.2014; Springer
• Subjects: Analysis; Contrast media; High performance liquid chromatography; Medicine; Methods of Analysis and Process Control; Organic Chemistry; Pharmacology/Toxicology; Pharmacy; Quality management; Structure of Chemical Compounds; iopromide; x-ray diffraction studies; proton magnetic resonance (PMR); conformer; thin-layer chromatography (TLC); quantum chemistry; conformational studies; high-performance liquid chromatography (HPLC); atropisomer
• ISSN: 0091-150X; 1573-9031
• DOI: 10.1007/s11094-014-1075-x

The atropisomer composition of iopromide substance and formulations is discussed. At 120 °C in aqueous iopromide solution, its atropisomers were found to be converted to conformers, which reached equilibrium with each other in 15 min at this temperature. Thus, the atropisomer composition of iopromide substance in solutions prepared using the technical method as described inevitably consists of the equilibrium between conformers formed at 120 °C. The equilibrium composition of these solutions persists after cooling, i.e., after return of conformers to the state of atropisomers. The relative content of the E 1 and E 2 (USP terminology) atropisomers (Σ E ) is an important quality indicator for iopromide formulations; only compliance with the inequality Σ E ≥ 20 % guarantees phase stability of solutions with working concentrations of iopromide ( ≤ 769 mg/ml) over a wide range of temperatures (0 – 120 °C). The inequality Σ E ≥ 20 % is inevitably reached during heat sterilization of iopromide.