Author
Phenomenex
Phenomenex
Phenomenex is a global technology leader committed to developing novel analytical chemistry solutions that solve the separation and purification challenges of researchers in industrial, government and academic laboratories.
Tags
Article
Academy
LinkedIn Logo

I am getting low recovery in my SPE method, how do I fix the problem?

We, 17.9.2025
| Original article from: Phenomenex
Practical troubleshooting guide for low recovery in SPE methods. Learn how to identify problems with solvents, flow rate, pH, or sorbent choice step by step.
<p><strong>Phenomenex: </strong>I am getting low recovery in my SPE method, how do I fix the problem?</p>

Phenomenex: I am getting low recovery in my SPE method, how do I fix the problem?

If you are working with an established method, we would recommend for you to:

  • Check all solutions used for the SPE method to ensure that nothing is expired or has been mislabelled.
  • Check the process. Was flow potentially too fast during loading or elution? Could the cartridges have been allowed to dry between equilibration and sample loading?

It is generally quickest to simply repeat the extraction, taking care of these points.

If, however, you are developing a new method, it might be necessary to “track down” your analyte. The first thing we would recommend is to make up a solution of the analyte without sample matrix (to use as an ideal sample). Then work through the sample method capturing the eluent from each step potentially containing the analyte:

  1. Condition the cartridge.
  2. Equilibrate the cartridge.
  3. Load the sample and collect the flow-through in a vial.
  4. Analyze this for analyte content. If analyte is found in this fraction it would suggest:
    • Sample solvent is too strong, or the pH is incorrect.
    • Loading flow rate is too high.
    • You have breakthrough because either sample load is too high, or sorbent mass is too low.
  5. Wash the cartridge, collecting each wash fraction in a separate vial.
  6. Again, analyze for analyte content. If analyte is found in any wash fraction, this suggests:
    • Wash solvent is too strong.
    • Wash solvent is not at the correct pH.
  7. If the analyte has not been found in the load or wash fractions, then the analyte must be retained on the cartridge.
    • Try using a stronger elution solvent.
    • Ensure pH of the elution solvent is correct.
    • If the first 2 suggestions don’t help, try using a less retentive sorbent (in reversed phase, try switching a C18 cartridge for a C8 if the analytes are very hydrophobic).
Phenomenex
LinkedIn Logo
 

Related content

Early-stage drug metabolite quantitation without radiolabels

Applications
| 2026 | Thermo Fisher Scientific
Instrumentation
HPLC, LC/MS, LC/SQ
Manufacturer
Thermo Fisher Scientific
Industries
Pharma & Biopharma, Metabolomics

Oligonucleotide Analysis Using the Agilent InfinityLab Pro iQ and Altura Oligo HPH-C18 Column

Applications
| 2026 | Agilent Technologies
Instrumentation
LC/MS, LC/SQ, Consumables, LC columns
Manufacturer
Agilent Technologies
Industries
Pharma & Biopharma

Simultaneous Quantitation and Discovery analysis: Combining targeted and untargeted metabolomics on Orbitrap mass spectrometers

Applications
| 2026 | Thermo Fisher Scientific
Instrumentation
LC/MS, LC/MS/MS, LC/Orbitrap, LC/HRMS
Manufacturer
Thermo Fisher Scientific
Industries
Metabolomics

Analysis of Per- and Polyfluoroalkyl Substances (PFAS) in Wastewater

Applications
| 2026 | Agilent Technologies
Instrumentation
LC/MS, LC/MS/MS, LC/QQQ
Manufacturer
Agilent Technologies
Industries
Environmental

Non-Targeted Screening of Biosolids with the Xevo™ MRT Mass Spectrometer Reveals New Isoforms of PFAS

Applications
| 2026 | Waters
Instrumentation
LC/MS, LC/MS/MS, LC/TOF, LC/HRMS
Manufacturer
Waters
Industries
Environmental
 

Related articles

News from LabRulezLCMS Library - Week 12, 2025
Article | Application

News from LabRulezLCMS Library - Week 12, 2025

This week we bring you application notes by Agilent Technologies, Knauer, Shimadzu and Waters Corporation and technical notes by ALS Europe and Thermo Fisher Scientific!
LabRulez
tag
share
more
All My Analytes are Neutrals, but Contaminants are Acids or Amines. What is the Best Way to Concentrate and Clean Up my Analytes of Interest?
Article | Academy

All My Analytes are Neutrals, but Contaminants are Acids or Amines. What is the Best Way to Concentrate and Clean Up my Analytes of Interest?

How can neutral analytes be efficiently concentrated in the presence of ionized acidic or basic contaminants? This SPE tip explains how mixed-mode cartridges improve selectivity and cleanup.
Phenomenex
tag
share
more
Troubleshooting SPE
Article | Academy

Troubleshooting SPE

A technical guide to troubleshooting low analyte recovery in SPE. Explains relative vs. absolute recovery and provides practical solutions for conditioning, loading, and sorbent selection.
Phenomenex
tag
share
more
SPE Troubleshooting - Extra Peak
Article | Academy

SPE Troubleshooting - Extra Peak

An SPE technical tip focused on identifying the sources of interferences and extra peaks observed after sample extraction.
Phenomenex
tag
share
more
 

Related content

Early-stage drug metabolite quantitation without radiolabels

Applications
| 2026 | Thermo Fisher Scientific
Instrumentation
HPLC, LC/MS, LC/SQ
Manufacturer
Thermo Fisher Scientific
Industries
Pharma & Biopharma, Metabolomics

Oligonucleotide Analysis Using the Agilent InfinityLab Pro iQ and Altura Oligo HPH-C18 Column

Applications
| 2026 | Agilent Technologies
Instrumentation
LC/MS, LC/SQ, Consumables, LC columns
Manufacturer
Agilent Technologies
Industries
Pharma & Biopharma

Simultaneous Quantitation and Discovery analysis: Combining targeted and untargeted metabolomics on Orbitrap mass spectrometers

Applications
| 2026 | Thermo Fisher Scientific
Instrumentation
LC/MS, LC/MS/MS, LC/Orbitrap, LC/HRMS
Manufacturer
Thermo Fisher Scientific
Industries
Metabolomics

Analysis of Per- and Polyfluoroalkyl Substances (PFAS) in Wastewater

Applications
| 2026 | Agilent Technologies
Instrumentation
LC/MS, LC/MS/MS, LC/QQQ
Manufacturer
Agilent Technologies
Industries
Environmental

Non-Targeted Screening of Biosolids with the Xevo™ MRT Mass Spectrometer Reveals New Isoforms of PFAS

Applications
| 2026 | Waters
Instrumentation
LC/MS, LC/MS/MS, LC/TOF, LC/HRMS
Manufacturer
Waters
Industries
Environmental
 

Related articles

News from LabRulezLCMS Library - Week 12, 2025
Article | Application

News from LabRulezLCMS Library - Week 12, 2025

This week we bring you application notes by Agilent Technologies, Knauer, Shimadzu and Waters Corporation and technical notes by ALS Europe and Thermo Fisher Scientific!
LabRulez
tag
share
more
All My Analytes are Neutrals, but Contaminants are Acids or Amines. What is the Best Way to Concentrate and Clean Up my Analytes of Interest?
Article | Academy

All My Analytes are Neutrals, but Contaminants are Acids or Amines. What is the Best Way to Concentrate and Clean Up my Analytes of Interest?

How can neutral analytes be efficiently concentrated in the presence of ionized acidic or basic contaminants? This SPE tip explains how mixed-mode cartridges improve selectivity and cleanup.
Phenomenex
tag
share
more
Troubleshooting SPE
Article | Academy

Troubleshooting SPE

A technical guide to troubleshooting low analyte recovery in SPE. Explains relative vs. absolute recovery and provides practical solutions for conditioning, loading, and sorbent selection.
Phenomenex
tag
share
more
SPE Troubleshooting - Extra Peak
Article | Academy

SPE Troubleshooting - Extra Peak

An SPE technical tip focused on identifying the sources of interferences and extra peaks observed after sample extraction.
Phenomenex
tag
share
more
 

Related content

Early-stage drug metabolite quantitation without radiolabels

Applications
| 2026 | Thermo Fisher Scientific
Instrumentation
HPLC, LC/MS, LC/SQ
Manufacturer
Thermo Fisher Scientific
Industries
Pharma & Biopharma, Metabolomics

Oligonucleotide Analysis Using the Agilent InfinityLab Pro iQ and Altura Oligo HPH-C18 Column

Applications
| 2026 | Agilent Technologies
Instrumentation
LC/MS, LC/SQ, Consumables, LC columns
Manufacturer
Agilent Technologies
Industries
Pharma & Biopharma

Simultaneous Quantitation and Discovery analysis: Combining targeted and untargeted metabolomics on Orbitrap mass spectrometers

Applications
| 2026 | Thermo Fisher Scientific
Instrumentation
LC/MS, LC/MS/MS, LC/Orbitrap, LC/HRMS
Manufacturer
Thermo Fisher Scientific
Industries
Metabolomics

Analysis of Per- and Polyfluoroalkyl Substances (PFAS) in Wastewater

Applications
| 2026 | Agilent Technologies
Instrumentation
LC/MS, LC/MS/MS, LC/QQQ
Manufacturer
Agilent Technologies
Industries
Environmental

Non-Targeted Screening of Biosolids with the Xevo™ MRT Mass Spectrometer Reveals New Isoforms of PFAS

Applications
| 2026 | Waters
Instrumentation
LC/MS, LC/MS/MS, LC/TOF, LC/HRMS
Manufacturer
Waters
Industries
Environmental
 

Related articles

News from LabRulezLCMS Library - Week 12, 2025
Article | Application

News from LabRulezLCMS Library - Week 12, 2025

This week we bring you application notes by Agilent Technologies, Knauer, Shimadzu and Waters Corporation and technical notes by ALS Europe and Thermo Fisher Scientific!
LabRulez
tag
share
more
All My Analytes are Neutrals, but Contaminants are Acids or Amines. What is the Best Way to Concentrate and Clean Up my Analytes of Interest?
Article | Academy

All My Analytes are Neutrals, but Contaminants are Acids or Amines. What is the Best Way to Concentrate and Clean Up my Analytes of Interest?

How can neutral analytes be efficiently concentrated in the presence of ionized acidic or basic contaminants? This SPE tip explains how mixed-mode cartridges improve selectivity and cleanup.
Phenomenex
tag
share
more
Troubleshooting SPE
Article | Academy

Troubleshooting SPE

A technical guide to troubleshooting low analyte recovery in SPE. Explains relative vs. absolute recovery and provides practical solutions for conditioning, loading, and sorbent selection.
Phenomenex
tag
share
more
SPE Troubleshooting - Extra Peak
Article | Academy

SPE Troubleshooting - Extra Peak

An SPE technical tip focused on identifying the sources of interferences and extra peaks observed after sample extraction.
Phenomenex
tag
share
more
 

Related content

Early-stage drug metabolite quantitation without radiolabels

Applications
| 2026 | Thermo Fisher Scientific
Instrumentation
HPLC, LC/MS, LC/SQ
Manufacturer
Thermo Fisher Scientific
Industries
Pharma & Biopharma, Metabolomics

Oligonucleotide Analysis Using the Agilent InfinityLab Pro iQ and Altura Oligo HPH-C18 Column

Applications
| 2026 | Agilent Technologies
Instrumentation
LC/MS, LC/SQ, Consumables, LC columns
Manufacturer
Agilent Technologies
Industries
Pharma & Biopharma

Simultaneous Quantitation and Discovery analysis: Combining targeted and untargeted metabolomics on Orbitrap mass spectrometers

Applications
| 2026 | Thermo Fisher Scientific
Instrumentation
LC/MS, LC/MS/MS, LC/Orbitrap, LC/HRMS
Manufacturer
Thermo Fisher Scientific
Industries
Metabolomics

Analysis of Per- and Polyfluoroalkyl Substances (PFAS) in Wastewater

Applications
| 2026 | Agilent Technologies
Instrumentation
LC/MS, LC/MS/MS, LC/QQQ
Manufacturer
Agilent Technologies
Industries
Environmental

Non-Targeted Screening of Biosolids with the Xevo™ MRT Mass Spectrometer Reveals New Isoforms of PFAS

Applications
| 2026 | Waters
Instrumentation
LC/MS, LC/MS/MS, LC/TOF, LC/HRMS
Manufacturer
Waters
Industries
Environmental
 

Related articles

News from LabRulezLCMS Library - Week 12, 2025
Article | Application

News from LabRulezLCMS Library - Week 12, 2025

This week we bring you application notes by Agilent Technologies, Knauer, Shimadzu and Waters Corporation and technical notes by ALS Europe and Thermo Fisher Scientific!
LabRulez
tag
share
more
All My Analytes are Neutrals, but Contaminants are Acids or Amines. What is the Best Way to Concentrate and Clean Up my Analytes of Interest?
Article | Academy

All My Analytes are Neutrals, but Contaminants are Acids or Amines. What is the Best Way to Concentrate and Clean Up my Analytes of Interest?

How can neutral analytes be efficiently concentrated in the presence of ionized acidic or basic contaminants? This SPE tip explains how mixed-mode cartridges improve selectivity and cleanup.
Phenomenex
tag
share
more
Troubleshooting SPE
Article | Academy

Troubleshooting SPE

A technical guide to troubleshooting low analyte recovery in SPE. Explains relative vs. absolute recovery and provides practical solutions for conditioning, loading, and sorbent selection.
Phenomenex
tag
share
more
SPE Troubleshooting - Extra Peak
Article | Academy

SPE Troubleshooting - Extra Peak

An SPE technical tip focused on identifying the sources of interferences and extra peaks observed after sample extraction.
Phenomenex
tag
share
more
Other projects
GCMS
ICPMS
Follow us
FacebookX (Twitter)LinkedInYouTube
More information
WebinarsAbout usContact usTerms of use
LabRulez s.r.o. All rights reserved. Content available under a CC BY-SA 4.0 Attribution-ShareAlike