Challenge Accepted: Arc Premier System Increases Sensitivity and Reproducibility for Hard-to-See Compounds

Importance of the Topic

Metal-sensitive compounds such as phosphate-containing analytes tend to adsorb onto metal surfaces in conventional LC systems, leading to poor peak shape, low sensitivity, and variable quantitation. Inert chromatographic surfaces are therefore critical for accurate and reproducible analysis in pharmaceutical, biochemical, and quality control laboratories.

Objectives and Study Overview

• Use adenosine nucleotides to probe surface inertness and assess detection limits
• Demonstrate performance improvements for steroid phosphate drug analysis
• Evaluate transferability of a reversed-phase method for non-metal-sensitive compounds across different LC platforms

Methodology

Reversed-phase LC separations were compared on three configurations:

• Standard stainless-steel system with SS columns
• Standard biocompatible MP35N system with SS columns
• Waters Arc Premier System with MaxPeak Premier Columns

Analytes included adenosine, ATP, ADP, AMP; hydrocortisone phosphate, betamethasone phosphate, dexamethasone phosphate, dexamethasone, dexamethasone acetate; and a mixture of seven non-metal-sensitive compounds. Mobile-phase gradients and detection settings were held constant for fair comparison.

Used Instrumentation

• Waters Arc Premier System
• MaxPeak Premier Columns with High Performance Surfaces Technology
• Standard stainless-steel and MP35N LC systems
• Empower 3 FR5 chromatography data system

Main Results and Discussion

• Adenosine nucleotides were detected at concentrations as low as 0.5 µg/mL with Gaussian peaks on the Arc Premier System, while traditional systems did not detect ATP or ADP below 25 µg/mL and showed significant tailing.
• Over 100 injections, the Arc Premier System maintained stable peak areas for ATP and ADP, whereas standard systems exhibited signal evolution due to surface interactions.
• Steroid phosphate drugs at low levels (1 µg/mL) produced sharp, symmetric peaks and low peak area RSD (<0.3 %) on the Arc system, enabling linear quantitation with less than 2.6 % deviation; standard systems showed up to 22 % quantitation error.
• Non-metal-sensitive compound mixtures displayed equivalent retention times and precision (%RSD <1 %) across all three systems, confirming seamless method transfer.

Benefits and Practical Applications

• Minimizes metal-analyte interactions for enhanced sensitivity and reproducibility of challenging assays
• Delivers improved peak shape and quantitation accuracy, reducing uncertainty in drug analysis
• Supports straightforward method transfers for routine analyses of non-metal-sensitive compounds

Future Trends and Opportunities

Advances in high-performance surface chemistries integrated with mass spectrometry and new stationary-phase technologies will broaden application scope in metabolomics, proteomics, and trace-level drug monitoring. Continued development of inert materials promises greater robustness and efficiency in regulated environments.

Conclusion

The Arc Premier System paired with MaxPeak Premier Columns effectively suppresses metal-analyte interactions, enabling lower detection limits, stable performance, and accurate quantitation for metal-sensitive compounds, while also providing comparable chromatographic performance for non-metal-sensitive analyses. This combination is a versatile solution for both routine and advanced LC workflows.

Reference

1. Tanna N., Plumb R., Mullin L. Improvements in Sensitivity for Quantification of Steroid Phosphate Drugs Using ACQUITY Premier System and ACQUITY Premier Columns. Waters Application Note 720007095EN, 2021.
2. Jung M., Lauber M. Demonstrating Improved Sensitivity and Dynamic Range with MaxPeak High Performance Surface (HPS) Technology: A Case Study on the Detection of Nucleotides. Waters Application Note 720007053EN, 2020.
3. Lauber M., Walter T.H., Gilar M., Delano M., Boissel C., Smith K., Birdsall R., Rainville P., Belanger J., Wyndham K. Low Adsorption HPLC Columns Based on MaxPeak High Performance Surfaces. Waters White Paper 720006930EN, 2020.
4. Patel A., Simeone J., Rzewuski S., Jung M., Lauber M. Premier Standards to Investigate the Inertness of Chromatographic Surfaces. Waters Application Note 720007105EN, 2021.
5. Cevc G., Blume G. Hydrocortisone and Dexamethasone in Deformable Drug Carriers Have Increased Biological Potency, Prolonged Effect, and Reduced Therapeutic Dosage. Biochimica et Biophysica Acta (BBA) – Biomembranes, 2004, 663(1-2), 61-73.