The ACQUITY RDa Detector Combined With RemoteAnalyzer Software to Give Simple, Rapid Accurate Mass Information in a Walk-Up Environment

Significance of the topic

The ability to obtain high‐resolution accurate mass data in a walk‐up setting addresses a critical need in synthetic chemistry labs, where rapid confirmation of active pharmaceutical ingredients (APIs) and related impurities accelerates decision making and reduces the risk of misassignment.

Objectives and Study Overview

This work demonstrates how the ACQUITY RDa Time‐of‐Flight detector paired with SpectralWorks’ RemoteAnalyzer browser interface offers a streamlined platform for routine accurate mass measurement. A model case involving ramipril spiked with trace impurities highlights the system’s capacity to deliver reliable mass confirmation with minimal user expertise.

Methodology and Used Instrumentation

A ramipril standard was prepared at 1 mg/mL in methanol and spiked at 0.1% w/w with four European Pharmacopeial impurity standards. Samples were analyzed on an ACQUITY UPLC I-Class PLUS with a BEH C18 column (50 × 2.1 mm, 1.7 μm) at 80 °C using a rapid 4 minute gradient (2 mM ammonium formate/0.1% formic acid vs. acetonitrile/0.1% formic acid). The ACQUITY RDa detector acquired positive‐mode full scan data from m/z 50–2000 with a 1.5 kV capillary voltage and 30 V cone voltage. Sample submission and batch control were managed via RemoteAnalyzer, while UNIFI handled data acquisition and waters_connect provided informatics integration.

Results and Discussion

Optimizing the column temperature to 80 °C resolved peak broadening and co-elution observed at lower temperatures. The fast scanning RDa detector maintained mass accuracy within ±2 ppm for the API and all four impurities, despite slight chromatographic overlap. Automated email notifications and interactive PDF or .swrc reports enabled users to review TICs, extracted ion chromatograms (EICs), and mass spectra remotely, ensuring timely interpretation of reaction outcomes.

Benefits and Practical Applications

• Accessible high-resolution mass confirmation for routine QC of APIs and degradants.
• Fast UPLC gradients without sacrificing mass accuracy, shortening turnaround times.
• Remote sample submission and automated reporting enhance lab workflow and data security.
• Role-based access in RemoteAnalyzer supports multi-user environments.

Future Trends and Possibilities for Application

Integration of walk-up HRMS tools with cloud-based informatics will further democratize access to accurate mass data. Emerging AI-driven interpretation algorithms may automate structural assignments and impurity profiling, while expanded connectivity can link real‐time analytics with process control in continuous manufacturing.

Conclusion

The combination of ACQUITY RDa and RemoteAnalyzer provides synthetic chemists with a user‐friendly, rapid HRMS solution. Reliable detection of ramipril and trace impurities in under five minutes demonstrates the platform’s suitability for routine mass confirmation without specialized expertise.

References

1. A Review of Waters Hybrid Particle Technology. Part 2: Ethylene Bridged (BEH) Hybrids for High-Temperature LC.
2. Alelyunas YW, Wrona MD, Cook K, McDonald S, Rainville P. Effect of MS Scan Speed on UPLC Peak Separation and Metabolite Identification: Time-of-Flight HRMS vs. Orbitrap.