Automated Screening for Pharma Process Development Workflows with the Waters ACQUITY™ RDa™ Detector, RemoteAnalyzer® and AnalyzerPro® XD

Significance of the Topic

High resolution accurate mass measurements are crucial for rapid characterization of pharmaceutical intermediates and impurities during drug development workflows.
Accessible HRMS platforms streamline decision making for synthetic chemists by providing reliable data without specialized expertise.

Study Objectives and Overview

This work demonstrates an automated platform combining the ACQUITY RDa detector with RemoteAnalyzer and AnalyzerPro XD software to support both targeted and untargeted screening of stressed samples.
A forced degradation study on the anti diabetic drug glipizide under acidic, basic and oxidative conditions illustrates the system capabilities.

Methodology and Used Instrumentation

Sample submission and data acquisition were performed on a waters_connect platform using ACQUITY RDa high resolution mass detector.
RemoteAnalyzer provided a user friendly interface for batch or plate submission and automated peak detection workflows.
Transferred data were processed offline in AnalyzerPro XD with defined thresholds, adduct lists and molecular files for known degradants.

• Instrument Waters ACQUITY RDa Detector
• Software waters_connect 4.0.0 RemoteAnalyzer v4.61 AnalyzerPro XD v1.16
• Sample Glipizide stressed under acid base and oxidation
• Workflow Targeted EIC for glipizide m/z 446.18565 and untargeted peak picking

Main Results and Discussion

Automated peak detection identified 3 peaks in acidic and oxidative samples and 8 peaks in base degradation including the parent API.
Accurate mass errors for identified components were below 5 ppm after instrument recalibration except one outlier at 6.14 ppm which prompted corrective action.
Unknown peaks were interrogated by elemental composition and online library search enabling identification of cyclohexylamine as a known degradant.
Complex base degradation by products without library matches highlight the need for advanced pathway prediction tools.

Benefits and Practical Applications

• Non expert users gain access to high resolution mass data via intuitive push button setup
• Integrated software enables high throughput sample submission and rapid result reporting by email or ELN export
• Combined targeted and untargeted analysis accelerates process optimization and impurity profiling
• Real time instrument monitoring through mass accuracy alerts and simple recalibration

Future Trends and Potential Applications

Advances in open access software and HRMS interfaces will expand adoption in quality control and scale up chemistry.
Integration with predictive degradation models and cloud based libraries will further enhance unknown identification.
Automated workflows for reaction monitoring and real time decision making will become standard in pharmaceutical process development.

Conclusion

The combination of the ACQUITY RDa detector with RemoteAnalyzer and AnalyzerPro XD delivers an accessible high resolution mass spectrometry platform for both targeted and untargeted screening.
This workflow simplifies data acquisition and interpretation for process chemists improving efficiency in drug development workflows and ensuring confidence in impurity profiling.

References

1. Termopoli V et al Mass Spectrometry Based Approach for Organic Synthesis Monitoring Analytical Chemistry 2019 91 11916-11922
2. Fontana A et al Automated open access LC-HRMS to support drug discovery projects Journal of Pharmaceutical and Biomedical Analysis 2020 178 112908
3. Beccaria M Cabooter D Current developments in LC-MS for pharmaceutical analysis Analyst 2020 145 1129-1157
4. Henry C Rainville P Targeted and Non-Targeted Identification and Characterization of Forced Degradation Products of Glipizide Using ACQUITY RDa Detector and UNIFI Software Workflows Application Note 720007510 February 2022
5. Albu M Medvedovici A Tache F HPLC-DAD Assay of Cyclohexylamine as Related Impurity in Glipizide Through Derivatization with O-Phthaldialdehyde Analytical Letters 2010 43 1162-1171