ISOLUTE® SLE+ User Guide (Supported Liquid Extraction)

Importance of the Topic

Supported liquid extraction (SLE) with ISOLUTE® SLE+ provides a streamlined alternative to traditional liquid–liquid extraction and protein precipitation, offering high analyte recovery, minimal matrix effects, and clean extracts suitable for LC-MS/MS analysis. Its application ranges across bioanalytical workflows, including drug monitoring, clinical studies, and high-throughput screening.

Objectives and Article Overview

This user guide aims to support the development and optimization of SLE methods using ISOLUTE® SLE+ products. It presents the extraction mechanism, compares extract cleanliness with other techniques, offers method development strategies for neutral, acidic, and basic analytes, and details automation and scalability options. A comprehensive application listing demonstrates real-world uses.

Methods and Instrumentation

• Sample preparation: simple load-wait-elute procedure using a diatomaceous earth support.
• Solvents: common water-immiscible solvents (MTBE, ethyl acetate, dichloromethane) with optional polar modifiers.
• pH control: acidic, basic, or neutral buffers to optimize analyte partitioning based on pKa.
• Instrumentation:
  • ISOLUTE® SLE+ plates and columns (10 µL–10 mL capacity).
  • VacMaster vacuum manifolds and PRESSURE+ positive-pressure manifolds for manual processing.
  • Biotage® Extrahera™ for automated high-throughput extraction.
  • TurboVap® systems for solvent evaporation.
• Analytical detection: LC-MS/MS and GC-MS for quantitative and qualitative analysis.

Main Results and Discussion

• SLE mimics repeated liquid–liquid extraction without emulsions, providing higher and more reproducible recoveries for diverse analytes including antidepressants, β-blockers, steroids, and cannabinoids.
• Inherent phospholipid and protein removal yields lower ion suppression and improved sensitivity versus protein precipitation and dedicated phospholipid depletion products.
• Scalability demonstrated consistent recoveries across sample volumes (200 µL–10 mL) and formats.
• Advanced strategies such as pH manipulation, ion pairing, and protein binding disruption extend the method to polar acids, strongly protein-bound compounds, and glucuronide conjugates.

Benefits and Practical Applications

• Rapid and simple workflow reduces manual steps and eliminates centrifugation or mixing, increasing laboratory throughput.
• Wide solvent compatibility and flexible pH control accommodate a broad analyte range.
• Automation compatibility enhances reproducibility and decreases processing time by up to 33% versus manual methods.
• Clean extracts improve sensitivity, lower quantitation limits, and reduce instrument maintenance.

Future Trends and Potential Applications

Further integration with automated platforms and miniaturized formats will drive high-throughput bioanalysis. Emerging applications include personalized medicine, complex matrices such as dried blood spots, and coupling to novel detection technologies. Volatile ion-pair strategies may expand scope to challenging metabolites and conjugates.

Conclusion

ISOLUTE® SLE+ offers a versatile, high-performance alternative to traditional extraction techniques. Its robust mechanism, ease of automation, and broad applicability make it a valuable tool for modern bioanalytical workflows seeking high sensitivity and throughput.

References

• ISOLUTE® SLE+ User Guide, Biotage, 2016.
• Biotage Application Notes and Technical Literature.