UTILIZING A COMPACT BENCHTOP TIME OF FLIGHT MASS SPECTROMETER FOR RAPID ACCURATE MASS INFORMATION IN A WALK-UP ENVIRONMENT

Importance of the topic

Accurate mass determination is essential for unambiguous identification of synthetic targets, by-products and impurities in organic chemistry workflows. Traditional single quadrupole instruments deliver nominal mass data that may lead to incorrect assignments. Compact high-resolution Time-of-Flight (ToF) mass spectrometers bridge this gap, providing rapid, precise mass measurements in a walk-up environment accessible to non-specialists.

Study objectives and overview

This work demonstrates a streamlined workflow combining a benchtop ToF instrument with browser-based sample submission and data review software. A four-minute UPLC-ToF method was used to analyze ramipril and four structurally related impurities at 0.1% levels. The goal was to prove routine high-resolution mass capability for synthetic chemists in a shared-use setting.

Methodology and instrumentation

Sample preparation involved spiking ramipril with ramipril isopropyl ester, diketopiperazine, methyl ester and hexahydroramipril. An ACQUITY RDa detector on a Waters UPLC platform acquired full-scan accurate mass data. Key LC-MS parameters included a four-minute gradient and ToF settings of 1.5 kV capillary voltage and 30 V cone voltage. Sample submission and processing were managed by RemoteAnalyzer software; data acquisition and raw file integrity were maintained via the UNIFI application on waters_connect.

Used instrumentation

• UPLC system with ACQUITY RDa Detector (Waters Corporation)
• UNIFI software within waters_connect platform
• RemoteAnalyzer web-based sample submission (SpectralWorks Ltd.)
• Barcode scanner for automated sample tracking

Main results and discussion

The five components were separated and detected within a four-minute runtime. Total ion chromatograms showed clean peaks for each analyte. All measured masses fell within ±2 ppm of theoretical values. Despite minor co-elution of the isopropyl ester and ramipril, high-resolution ToF data enabled accurate deconvolution and quantitation. Automated detector setup, tuning, and calibration allowed non-expert operation.

Benefits and practical applications of the method

• Rapid access to high-resolution mass data for routine synthesis verification
• Confidence in compound identity and impurity profiling at trace levels
• Minimal operator expertise required due to automated tuning and browser-based workflow
• Reduced analysis time with four-minute UPLC run and immediate email notification of results

Future trends and potential applications

Integration of AI-driven spectral interpretation and database matching can further simplify data review. Expanding browser-based platforms to multi-instrument networks will support high-throughput labs. Continued miniaturization and software automation will drive adoption in academic and industrial settings for routine QA/QC, metabolite screening and reaction monitoring.

Conclusion

The combination of a compact benchtop ToF instrument and web-based software delivers accurate mass measurements in minutes with minimal training. This workflow empowers synthetic chemists to make fast, confident decisions regarding product identity and impurity profiles.

References

1. A Review of Waters Hybrid Particle Technology. Part 2: Ethylene Bridged [BEH Technology™] Hybrids and Their Use in Liquid Chromatography. 720001159EN
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. March 2013;720004762EN