Developing an improved UHPLC method for impurity profile analysis of ceftriaxone using analytical quality by design

Area of Science:

• Analytical Chemistry
• Pharmaceutical Sciences

Background:

• Traditional Chinese Pharmacopoeia (ChP) HPLC methods for ceftriaxone impurity analysis lack selectivity and are time-consuming.
• Existing methods struggle to comprehensively identify and quantify potential impurities in ceftriaxone formulations.

Purpose of the Study:

• To develop a novel reversed-phase ultra-high-performance liquid chromatography (UHPLC) method for comprehensive impurity profiling of ceftriaxone.
• To improve upon the limitations of existing ChP HPLC methods regarding selectivity and analysis time.

Main Methods:

• Method development based on ChP HPLC, involving screening experiments to identify critical parameters like octylamine concentration, mobile phase pH, and organic phase ratio.
• Optimization using Monte-Carlo simulations to define the design space for robust method performance.
• Validation using a multivariate approach to confirm method robustness and acetonitrile proportion control.

Main Results:

• A new UHPLC method achieved complete separation of ceftriaxone impurities within approximately 10 minutes.
• The method demonstrated robustness and identified critical parameters requiring careful control, such as acetonitrile proportion.
• Successful single-step transferability of the UHPLC method back to HPLC using a Columns Calculator was demonstrated.

Conclusions:

• The developed UHPLC method offers a rapid, selective, and robust approach for measuring ceftriaxone impurities.
• This method provides a significant advancement over current ChP HPLC methods, enhancing pharmaceutical quality control.
• The findings offer a valuable reference for future revisions of the Chinese Pharmacopoeia and rapid HPLC method development.