Chemical analysis of solid-state irradiated human insulin

Area of Science:

• Pharmaceutical Science
• Radiation Chemistry

Background:

• Radiosterilization is a common method for ensuring the sterility of pharmaceutical products.
• Understanding the chemical impact of irradiation on therapeutic proteins like human insulin is crucial for maintaining drug efficacy and safety.

Purpose of the Study:

• To investigate chemical modifications in solid human insulin following exposure to radiosterilization doses.
• To assess the impact of absorbed radiation dose on the radiolysis of human insulin.

Main Methods:

• Analysis of volatile radiolytic products using gas chromatography-mass spectrometry (GC-MS).
• Quantification of non-volatile products via high-performance liquid chromatography (HPLC), including size exclusion chromatography (SEC) for higher molecular weight proteins and reverse-phase HPLC-UV for related compounds.
• Assessment of conformational changes using circular dichroism (CD) spectroscopy.

Main Results:

• Gamma irradiation at 10 kGy resulted in 96.8% insulin recovery.
• Higher molecular weight proteins constituted only 0.35% and related compounds (e.g., A21 desamido insulin) 1.29% of the analyzed products.
• No significant structural alterations or detectable volatile radiolytic compounds were observed.

Conclusions:

• Human insulin irradiated in solid-state at 10 kGy (gamma) and 14 kGy (electron-beam) meets European Pharmacopoeia standards.
• Solid-state human insulin demonstrates considerable stability against radiation-induced chemical changes.