Development of a Simultaneous Analytical Method for Amines Corresponding to 10 Typical Nitrosamines

Area of Science:

• Pharmaceutical Analysis
• Chemical Contamination
• Regulatory Science

Background:

• Regulatory agencies worldwide are mandating risk assessments for nitrosamine contamination in pharmaceuticals.
• Current risk assessments rely on desk investigations, which may not identify all potential contamination sources.
• Nitrosamines form from amines and nitrosating agents; residual amines in Active Pharmaceutical Ingredients (APIs) are a potential source.

Purpose of the Study:

• To develop and validate a simultaneous analytical method for detecting residual amines in APIs.
• To provide a tool for identifying potential nitrosamine contamination risks not covered by desk investigations.

Main Methods:

• Development of a simultaneous analytical method for 10 typical small alkyl amines.
• Validation of the method for linearity, limit of quantitation, limit of detection, recovery, and repeatability.
• Testing the method's applicability across various APIs.

Main Results:

• The method demonstrated good linearity across specified ranges for different amines.
• Achieved low limits of quantitation (0.003 μg/mL) and detection (0.001-0.003 μg/mL).
• Showed acceptable recovery rates (70-130% for 121 APIs) and good repeatability (%RSD < 15%).

Conclusions:

• The validated analytical method effectively quantifies residual amines in APIs.
• This method can identify potential nitrosamine contamination risks missed by conventional assessments.
• The method is expected to contribute significantly to pharmaceutical risk assessment strategies for nitrosamine contamination.