Combining Multiple Acquisition Channels for Analysis of Impurities Using Empower 3 Software

Significance of the Topic

Detecting trace levels of genotoxic impurities is a critical aspect of pharmaceutical quality control. Single ion recording (SIR) in mass spectrometry offers exceptional sensitivity and selectivity for targeted compounds. However, monitoring multiple ions with different masses in a single sample often generates separate data channels, complicating data analysis and increasing processing time. Combining these channels into one result streamlines workflows and enhances quantitation accuracy.

Objectives and Overview

The primary aim of this study is to demonstrate how Empower 3 Chromatography Data Software (CDS) can merge multiple SIR acquisition channels collected during a single injection into a unified analytical result. The approach is illustrated using methyl, ethyl, and isopropyl esters of benzenesulfonic acid (MBS, EBS, IBS) as potential genotoxic impurities in an amlodipine besylate sample.

Methodology and Instrumentation

A sample containing 0.1 mg/mL of amlodipine besylate was spiked with each benzenesulfonic acid ester at a 0.1% level. Data acquisition was performed on an ACQUITY UPLC system coupled with a QDa mass detector. Four SIR channels were monitored simultaneously (m/z 190.1 for MBS, 204.1 for EBS, 218.1 for IBS, and 409.3 for the API). Empower 3 CDS applied a formula-based derived channel to mathematically combine these SIR traces into a single plot for analysis.

Used Instrumentation

• Empower 3 Chromatography Data Software (CDS)
• ACQUITY UPLC System
• QDa Mass Detector

Key Results and Discussion

The combined SIR channel produced one chromatogram displaying distinct peaks for the three esters and the API. This unified result enabled accurate quantitation of each impurity from a single injection, maintaining high sensitivity and selectivity. Data processing was significantly simplified compared to handling individual SIR channels, reducing the risk of integration errors and accelerating reporting.

Benefits and Practical Applications

• Reduces the number of injections and acquisition channels to manage.
• Streamlines data processing and minimizes manual integration steps.
• Increases sample throughput in routine QC and release testing.
• Ensures compliance with impurity specifications in drug development.

Future Trends and Applications

Future developments may integrate high-resolution mass spectrometry and machine learning algorithms for automated deconvolution of complex mixtures. Enhanced software automation and cloud-based CDS platforms will facilitate real-time data sharing, collaborative review, and streamlined regulatory submissions. The combination of multiple acquisition channels will extend to other analytical modes, supporting increasingly stringent safety requirements.

Conclusion

Empower 3 CDS provides a robust and flexible solution for combining multiple SIR channels into a single analytical result. This capability improves efficiency and reliability in the quantitation of low-level impurities, offering a valuable tool for pharmaceutical laboratories engaged in drug substance development and quality control.

References

1. Maziarz M., Wrona M., Coupling Mass Detection with UV to Improve Method Sensitivity for Esters of Benzenesulfonic Acid in Analysis of Genotoxic Impurities, Waters Application Note 720005680EN, 2016.