Simultaneous sampling of two product streams

Importance of the Topic

Efficient sampling in preparative HPLC, and especially in simulated moving bed (SMB) processes, is critical for accurate process control and rapid method development. Traditional sampling approaches suffer from large dead volumes and manual handling, delaying analysis and reducing accuracy at low flow rates.

Objectives and Overview

This study aimed to implement an 8-port two-position valve for simultaneous collection of extract and raffinate streams during SMB separation of caffeine and paracetamol. The goal was to streamline sampling, reduce dead volume, and accelerate method optimization.

Methodology

An AZURA Lab SMB system operated in a 2:2:2:2 configuration was used for separating caffeine and paracetamol. The 8-port valve was integrated downstream of the SMB zones to switch flow paths between product bottles and sample vessels. Samples were automatically taken for each of the first twelve cycles, and entire cycle fractions were also collected for comparison. Chromatograms of extract and raffinate streams were overlaid to monitor concentration profiles during process start-up.

Instrumentation

• AZURA Lab SMB system, biocompatible lab scale (Article A29100)
• Manual injection valve AZURA V 4.1, 8-port two-position (AVJ36AE)
• Mounting bracket for AZURA Lab (A9853)
• Flow meters: 3× M13 (A29800), 1× M12 (A5394)
• Columns: 8× Eurospher II C8, 150×8 mm, 100–15 µm
• Software: PurityChrom MCC (included in A29100)

Results and Discussion

The 8-port valve enabled simultaneous diversion of extract and raffinate flows to sample vessels without manual reconnection of tubing. Chromatograms showed steadily increasing paracetamol concentrations in the raffinate and caffeine in the extract during the first twelve cycles. Dead volume was minimized, resulting in faster sampling response and more accurate concentration measurements, even at low flow rates.

Benefits and Practical Applications

• Improved sampling precision and reduced delay volume enhance method development speed.
• Single-valve operation lowers equipment cost and bench footprint compared to dual-valve setups.
• Safer and simpler handling by eliminating manual tubing switches.

Future Trends and Opportunities

• Integration of online analytics (e.g., UV, MS) for real-time SMB monitoring.
• Automation of multi-component separations using advanced valve configurations.
• Scale-up potential for pilot and production SMB systems with minimal sampling dead volume.

Conclusion

The 8-port two-position sampling valve represents an elegant solution for simultaneous extract and raffinate sampling in SMB processes. It streamlines operations, reduces sample delay, and provides more reliable data for rapid method optimization.

References

• Stephan S., Krauke Y., Pietsch P., Monks K. Simultaneous sampling of two product streams. KNAUER Wissenschaftliche Geräte GmbH Application Note VTN0012, 05/2021.