Ultra-sensitive HPLC-ESI-MS/MS quantitation of N-nitroso-phenylephrine in phenylephrine-containing anticold products

Area of Science:

• Pharmaceutical Analysis
• Analytical Chemistry
• Drug Safety

Background:

• Phenylephrine, a common cold medication ingredient, can form N-nitroso-phenylephrine (NNPE), a potentially carcinogenic nitrosamine.
• Nitrosamine contamination in pharmaceuticals is a growing concern, yet specific methods for NNPE are lacking.

Purpose of the Study:

• To develop and validate a sensitive and selective analytical method for quantifying NNPE in phenylephrine-based cold medications.
• To assess the prevalence and levels of NNPE in commercial pharmaceutical products.

Main Methods:

• Development of a High-Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (HPLC-ESI-MS/MS) method.
• Method validation according to ICH Q2(R2) guidelines, including linearity, accuracy, precision, and low limits of detection (1.95 pg/mL) and quantification (3.9 pg/mL).
• Simple sample preparation involving direct aqueous dissolution and analysis using an isotopically labelled internal standard to mitigate matrix effects.

Main Results:

• The validated HPLC-ESI-MS/MS method demonstrated high sensitivity, selectivity, and reliability for NNPE determination.
• NNPE was detected in all analyzed commercial anticold products containing phenylephrine.
• Several products contained NNPE levels exceeding established acceptable intake limits.

Conclusions:

• The developed method is suitable for routine quality control and safety assessment of phenylephrine-containing pharmaceuticals.
• The findings indicate a need for monitoring NNPE contamination in cold medications.
• Ensuring pharmaceutical safety requires robust analytical tools for detecting potentially harmful impurities like NNPE.