ACQUITY™ RDa™ Detector with RemoteAnalyzer® Software for Open-access Mass Confirmation of Synthetic Targets

Importance of Topic

Accurate mass confirmation plays a critical role in medicinal chemistry by enabling rapid verification of synthetic targets and impurities. High resolution mass spectrometry combined with open-access workflows reduces misidentification risks and accelerates decision making in drug development.

Goals and Study Overview

This application note demonstrates a streamlined sample submission and analysis process using the ACQUITY RDa Detector integrated with the RemoteAnalyzer software. The objective is to provide both expert and non-expert users with a simple interface for targeted accurate mass screening of glipizide and its forced-degradation impurities.

Methodology and Instrumentation

The study employed an ACQUITY RDa Detector coupled to waters_connect software for data acquisition and RemoteAnalyzer v4.61.4678.0 for open-access control. A single manually submitted sample of acid-degraded glipizide was processed using the Target Confirmation workflow. Empirical formulas and adduct settings for glipizide and known impurities II and III were entered via the browser-based interface.

Main Results and Discussion

The platform delivered sub-5 ppm mass error confirmation for the glipizide API (2.57 ppm) and impurities II (0.66 ppm) and III (1.14 ppm). UV-aligned extracted ion chromatograms highlighted peak saturation for the API and in-source fragmentation leading to coelution of an impurity with the parent compound. The automated report paired UV traces with mass spectra for rapid interpretation.

Benefits and Practical Applications

• Routine access to accurate mass data for confident target identification
• Simple, walk-up sample submission requiring minimal expertise
• Browser-based control facilitating remote data review and sharing across sites
• Automated report generation compatible with email and electronic laboratory notebooks

Future Trends and Potential Uses

Open-access HRMS workflows are expected to become increasingly prevalent in high-throughput medicinal chemistry and QA QC laboratories. Integration with cloud informatics and automated impurity profiling will further reduce turnaround times and support decentralized drug discovery teams.

Conclusion

The combination of the ACQUITY RDa Detector with RemoteAnalyzer software simplifies accurate mass confirmation of synthetic drug candidates and their impurities. This platform delivers reliable sub-5 ppm mass accuracy via a user-friendly interface, promoting rapid decision making in drug development.

Reference

1. Deng G, Sanyal G. Applications of mass spectrometry in early stages of target based drug discovery. J Pharm Biomed Anal. 2006;40(3):528–538.
2. Fontana A et al. Automated open-access LC HRMS to support drug discovery projects. J Pharm Biomed Anal. 2020;178:112908.
3. Bansal G et al. LC and LC MS study on forced decomposition of glipizide. J Chromatogr Sci. 2008;46.
4. Henry C, Rainville P. Identification and characterization of glipizide degradation products. Waters application note 720007510. 2022.