Identification and structural characterization of four novel degradation products and a process impurity of isavuconazonium sulfate for injection formulation bulk by LC-ESI-QTOF-MS/MS

Abstract

Isavuconazonium sulfate is a highly water-soluble pro-drug of active triazole isavuconazole. The degradation profile of isavuconazonium sulfate for injection formulation bulk under acid hydrolysis, alkaline hydrolysis, oxidation, heat, and light conditions was studied using LC-PDA/MS technique. Four degradation products (DP1 to DP4) and one process impurity (PI1) were identified in isavuconazonium sulfate formulation bulk and characterized the identified impurities by liquid chromatography-electron spray ionization-quadruple-time of flight tandem mass spectrometry. Isavuconazole (DP1) was found to be one of the major degradation products of isavuconazonium sulfate.

Keywords

Characterization degradation products isavuconazonium sulfate LC-PDA/MS tandem mass spectrometry degradation profile

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References

Flick

Ding

Leverett

, et al. Synthetic approaches to the new drugs approved during 2015. J Med Chem 2017; 60: 6480–6515.

Ohwada

Tsukazaki

Hayase

, et al. Design, synthesis and antifungal activity of a novel water soluble prodrug of antifungal triazole. Bioorg Med Chem Lett 2003; 13: 191–196.

Murrell

Bossaer

Carico

, et al. Isavuconazonium sulfate: a triazole prodrug for invasive fungal infections. Int J Pharm Pract 2017; 25: 18–30.

European medicines agency, assessment report, EMA/596950/2015.

ICH Q1A (R2). Stability testing of new drug substances and products (step4). In: International conference on harmonization, Geneva, Switzerland, 2003.

ICH Q3A (R2). Impurities in new drug substances (step4). In: International conference on harmonization, Geneva, Switzerland, 2006.

ICH Q3B (R2). Impurities in new drug products (step4). In: International conference on harmonization, Geneva, Switzerland, 2006.

Astellas Pharma US, Inc. Cresemba (package insert). Northbrook. IL: Astellas Pharma Inc, 2018 (Revised).

ICH Q1B. Stability testing: photostability testing of new drug substances and product). In: International Conference on Harmonization, Geneva, Switzerland, 1996.

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