Solid Phase Extraction (SPE) Sorbent Selection for LC–MS / GC–MS Sample Preparation
Introduction
Solid Phase Extraction (SPE) is a critical step in modern analytical workflows, especially in environmental testing, food safety, pharmaceutical QC, toxicology and biological analysis.
Choosing the correct SPE sorbent directly determines:
• Extraction recovery
• Matrix cleanup efficiency
• Detection sensitivity
• Column lifespan
• Method reproducibility
However, many laboratories struggle to determine which sorbent best fits their analytes and matrices with so many SPE types, such as C18, Florisil, PSA, SAX, SCX, HLB and more.
This guide provides a step-by-step framework to help analysts select the ideal SPE column for LC-MS/GC-MS workflows.
Key Factors in SPE Sorbent Selection
1. Consider the Chemistry of Your Target Analytes
Ask these questions:
Are your analytes polar, non-polar, ionic, or mixed-functionality?
Are they weak acids, strong acids, weak bases, strong bases?
Are they likely to bind by hydrophobic, polar, or ionic interactions?
2. Consider the Sample Matrix
Different matrices generate different interference profiles:
Food samples → sugars, fats, pigments
Environmental samples → humic acids, organics
Biological samples → proteins, lipids
Pharmaceutical samples → excipients, degradation products
3. Consider the Analytical Method
• LC-MS/MS requires cleaner extracts than HPLC-UV
• GC-MS cleanup often prioritizes pigment and lipid removal
• Regulatory methods (EPA, AOAC, USP) may specify sorbents
SPE Sorbent Types Explained (Table Overview)
| Category | Sorbent Type | Key Features | Typical Applications |
|---|---|---|---|
| Reversed-Phase | C18 | Strong hydrophobic retention; high capacity | Pharmaceuticals, environmental organics, food extracts |
| C8 | Moderate hydrophobicity; faster elution | General cleanup, biological samples | |
| Normal-Phase | Silica | Polar interactions; versatile adsorption | Organic acids, pigments, polar compounds |
| Florisil | Magnesium silicate; strong for polar compounds | Pesticides (GC), environmental pollutants | |
| Ion Exchange | SAX | Strong anion exchange | Acidic compounds, environmental anions |
| SCX | Strong cation exchange | Basic drugs, alkaloids, amines | |
| NH₂ | Weak anion exchange + NP functionality | Carboxylic acids, sugars | |
| Mixed-Mode / Specialty | PSA | Removes sugars, fatty acids, pigments | Mycotoxins, QuEChERS pesticide cleanup |
| GCB | Adsorbs planar molecules | Pigments, polyaromatics | |
| HLB | Broad compatibility (hydrophilic + lipophilic) | Biological fluids, pharmaceuticals | |
| MCX | Mixed-mode cation exchange | Basic compounds in complex matrices | |
| MAX | Mixed-mode anion exchange | Acidic analytes in food/environment samples |
4. How to Choose the Right SPE Column (step-by-step Guide)
Step 1 - Identify the Analyte Chemistry
Non-polar analytes → C18
Moderately non-polar → C8
Strong acids → SAX
Weak acids → NH₂ or MAX
Strong bases → SCX or MCX
Pigmented samples → GCB
Sugars/fats interference → PSA
Step 2 - Assess the Matrix
Fruits, vegetables → PSA + GCB
Soil/water pollutants → C18, Florisil, NH₂
Plasma/serum → HLB or C18
Grains & nuts (mycotoxins) → PSA/HLB
Step 3 - Match to Method Requirements
GC-MS pesticide methods (EPA 8081/8082) → Florisil
Clean biomass samples for LC-MS → HLB
USP impurity tests → C18 / SCX
Step 4 - Evaluate Recovery & Cleanup Needs
If analytes:
Bind too strongly → Choose weaker sorbent (C8 over C18)
Elute poorly → Modify wash/elution solvents or choose mixed-mode sorbent
Are lost during cleanup → Reduce sorbent strength or switch to HLB
Step 5 - Consider Automation & Throughput
High-throughput labs benefit from:
• 96-well SPE plates
• Cartridges with consistent sorbent mass
• OEM sorbent packs for robots
SPE Sorbent Selection Examples (Real-World Scenarios)
Case 1: Pesticide Residues in Fruits
Recommended: PSA + GCB (QuEChERS style cleanup)
Why: Removes sugars, organic acids, pigments.
Case 2: Antibiotics in Milk
Recommended: HLB
Why: Mixed polarity analytes, complex matrix.
Case 3: PAHs in Environmental Water
Recommended: C18
Why: Strong hydrophobic retention improves concentration efficiency.
Case 4: Mycotoxins in Cereals
Recommended: PSA or HLB
Why: Removes lipids and pigments, high recovery for aflatoxins.
Case 5: Basic Pharmaceuticals in Plasma
Recommended: MCX (mixed-mode cation exchange)
Why: Strong retention + clean elution improves LC-MS signal.
Tips for Improving SPE Performance
1. Use 0.22 μm syringe filters to prevent sorbent clogging.
2. Adjust pH to control ionization of analytes (critical for SAX/SCX).
3. Condition → Load → Wash → Elute sequence must be optimized.
4. Avoid excessive washing, which may remove target analytes.
5. For LC-MS, use volatile buffers (ammonium acetate/formate).
Selecting the right SPE column is essential for achieving clean samples, reliable analytics and accurate LC-MS/GC-MS data. By understanding analyte chemistry, matrix type and analytical requirements, laboratories can significantly improve extraction performance and method robustness.
Our complete SPE sorbent portfolio ensures you always find the right tool for your application.
→ Contact our technical specialists
Olica Xu
