Organic Impurity Analysis of Cetirizine Hydrochloride Drug Material Following USP Monograph

Importance of the Topic

The analysis of organic impurities in pharmaceutical substances ensures safety, potency and compliance with regulatory standards. Cetirizine hydrochloride is a widely used second-generation antihistamine. Accurate impurity profiling is essential for drug quality control and regulatory approval.

Objectives and Study Overview

This study evaluates two official procedures described in USP 41 monograph for organic impurity analysis of cetirizine hydrochloride. Both methods were implemented on a Shimadzu i-Series LC-2050 HPLC system to assess suitability, sensitivity and impurity detection capability.

Methodology and Instrumentation

Parameters for each procedure:

• Procedure 1: Isocratic HPLC with Shim-pack UC-Sil column, mobile phase ACN/H2O/H2SO4 (93:6.6:0.4), UV detection at 230 nm
• Procedure 2: Gradient HPLC with Shim-pack GIST column, mobile phases phosphate buffer and methanol, UV detection at 232 nm

Instrument details:

• HPLC system: Shimadzu i-Series LC-2050
• Columns: UC-Sil (250×4.6 mm, 5 µm) and GIST (250×4.6 mm, 5 µm)
• Detectors: UV at 230 nm (Procedure 1) and 232 nm (Procedure 2)
• Flow rates: 1.0–1.5 mL/min; column oven at 40 °C

Key Results and Discussion

System suitability tests met all acceptance criteria:

• Area and retention time RSD below 2%
• Tailing factors within limits
• Theoretical plates above 6000

Impurity profiling results:

• Procedure 1 (500 µg/mL) detected three known impurities and six unknowns, all below 0.1% area
• Procedure 2 (2 mg/mL) identified five monograph impurities plus five unknowns; most unknown peaks below 0.1%, with one at 0.32%

Benefits and Practical Application

• High sensitivity and reproducibility for trace-level impurity detection
• Compliance with USP 41 ensures regulatory alignment for quality control
• Dual procedures allow flexibility for different impurity ranges and concentrations

Future Trends and Potential Applications

Ongoing developments may include:

• Integration of mass spectrometric detection for structural elucidation of unknowns
• Automated data processing workflows for rapid impurity screening
• Method transfer to ultra-high-performance LC for faster run times

Conclusion

The application of both USP 41 procedures on the Shimadzu i-Series LC-2050 system delivers robust, sensitive impurity profiles for cetirizine hydrochloride. System suitability criteria and impurity limits were met, confirming the methods suitability for routine quality control and regulatory testing.

Reference

1. United States Pharmacopeia USP 41 Official Monographs Cetirizine Hydrochloride Effective May 1 2018