BioTech Startup Advances Preclinical Studies for Topical Osteoarthritis Drug with Waters ACQUITY Premier System and Xevo TQ-XS

Importance of the Topic

Topical treatments for osteoarthritis pain reduce systemic side effects and improve patient outcomes. Reformulating potent NSAIDs like rofecoxib into a topical product can mitigate gastrointestinal and cardiovascular risks associated with oral use. Recent advances in LC-MS instrumentation enable sensitive quantitation of challenging compounds, accelerating preclinical studies and formulation optimization.

Objectives and Study Overview

BriOri BioTech aimed to repurpose rofecoxib into a topical formulation to deliver strong analgesic effect locally while minimizing systemic exposure. Key goals included enhancing skin penetration, reducing carryover in analytical assays, and demonstrating superior efficacy over oral competitors in preclinical models.

Methodology and Instrumentation

BriOri BioTech progressed from a used Waters 600 HPLC system to advanced UPLC-MS platforms to achieve required sensitivity and reproducibility:

• Early diffusion assays: Waters 600 HPLC with UV detection for membrane studies
• UPLC-MS screening: Waters ACQUITY QDa and Xevo TQD systems with Empower and MassLynx software
• High sensitivity analysis: Waters ACQUITY Premier UPLC with MaxPeak high performance surfaces and Xevo TQ-XS mass spectrometer featuring StepWave XS ion guide

Key Results and Discussion

Analytical improvements enabled robust quantitation at pg/mL levels with negligible carryover. Preclinical findings included:

• Threefold higher human skin penetration than market alternatives
• Greater AUC and Cmax with lower systemic exposure compared to oral dosing
• Enhanced synovial accumulation and superior pain relief at 8 and 24 hours post-application
• Zero skin irritation in mini-pig Draize tests

Benefits and Practical Applications

The combination of optimized formulation and advanced analytics allows for:

• Rapid preclinical turnaround and formulation decisions
• Minimized animal use through high-sensitivity detection
• Reduced development costs by leveraging existing FDA data via a 505(b)(2) pathway

Future Trends and Opportunities

Ongoing trends include the adoption of metal-passivated LC surfaces, expansion of topical delivery for other NSAIDs, and integration of high-resolution MS for metabolite profiling. Broader applications may arise in personalized topical therapies and in-field quality control using compact UPLC-MS systems.

Conclusion

BriOri BioTech’s work demonstrates that reformulating rofecoxib as a topical agent, coupled with state-of-the-art LC-MS technology, can deliver potent local analgesia with reduced systemic risks. The integration of Waters’ ACQUITY Premier and Xevo TQ-XS platforms proved critical to overcoming solubility and carryover challenges, accelerating the path to clinical trials.

References

1. Allied Market Research Topical Pain Relief Market Forecast to 2027.