Simultaneous analysis of drug substances according to USP assay and impurity methods

Significance of the Topic

The simultaneous determination of drug content and related impurities is critical in pharmaceutical quality control to accelerate product release, optimize laboratory workflow and minimize human error. Dual-channel LC systems address the demand for higher throughput and efficient bench space utilization in routine analysis.

Objectives and Study Overview

The study aims to demonstrate a reduction in analysis time by performing USP assay and impurity tests for esomeprazole magnesium in parallel on a Vanquish Flex Duo for Dual LC. The approach uses two independent flow paths with distinct mobile phases to meet monograph requirements in a single run.

Methodology

A dual UHPLC setup allowed concurrent execution of isocratic methods for assay and impurity determinations. Solution A comprised a phosphate buffer for assay and impurities, while solution B was an acetonitrile phosphate mix. Assay samples and standards at 0.05 mg/mL were prepared in methanol, buffer and water. Impurity samples were diluted in a solvent blend of buffer and acetonitrile. Detection was performed at 280 nm with data collection at 10 Hz.

Used Instrumentation

• Vanquish Flex Duo UHPLC with two independent flow paths
• Vanquish Dual Pump and Dual Split Sampler FT
• Vanquish Column Compartment H
• Two Vanquish Diode Array Detectors with semi micro flow cells (2.5 µL)
• Thermo Scientific Hypersil BDS C8 column (150 × 4.6 mm, 5 µm)
• Chromeleon 7.3.1 Chromatography Data System

Results and Discussion

Parallel operation met all USP system suitability criteria. For the assay method, six replicate injections yielded a tailing factor of 1.04, peak area RSD of 0.03% and retention time RSD of 0.04%. The sample contained 96.5% esomeprazole magnesium on anhydrous basis. In the impurity method, resolution between esomeprazole and its related compound A was 3.95. Three impurities were detected with signal to noise ratios above 10, and all individual and total impurity levels remained below USP limits.

Benefits and Practical Applications

• Doubling of throughput without additional instruments
• Efficient bench space and solvent usage
• Reduced analyst workload and potential errors
• Cost savings on maintenance and consumables

Future Trends and Potential Applications

The dual-path UHPLC concept can be extended to method development, robustness testing and mass balance studies requiring multiple detectors. Integration with automated sample handling and advanced detectors will further enhance flexibility and throughput in regulated laboratories.

Conclusion

The Vanquish Flex Duo for Dual LC enables simultaneous USP assay and impurity analysis of esomeprazole magnesium, achieving significant time savings and resource optimization while meeting stringent system suitability requirements.

References

1. Thermo Fisher Scientific BR72623 Brochure for Vanquish Duo UHPLC Systems
2. USP monograph of esomeprazole magnesium, official as of 01-May-2021
3. Dong Q Zhu J Sui Q et al Optimization of mobile phase and stress condition investigation by LC-MS J Sep Sci 2013 36 1200-1208