Why is isopropanol rarely used as a solvent in HPLC or LCMS methods - FAQ
April 14, 2020
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Date: 14-APRIL-2020   Last Updated: 9-JUNE-2025
While isopropanol (IPA) is a common laboratory solvent, it is infrequently used as a primary mobile phase component in HPLC or LC-MS methods. Here’s why:

1. Higher Viscosity = Higher Backpressure

IPA is significantly more viscous than commonly used solvents like acetonitrile (ACN) or methanol (MeOH). This increased viscosity leads to:

  • Higher system backpressure
  • Reduced flow rate flexibility
  • Potential strain on pumps and fittings

As a result, IPA is less practical for routine use, especially in high-throughput or high-pressure systems.


2. Limited Selectivity Advantages

In terms of chromatographic selectivity, IPA offers few unique benefits. When visualized in a solvent selectivity triangle (with ACN, MeOH, and tetrahydrofuran [THF] at the corners), IPA typically falls within the range achievable by blending these other solvents. Therefore, most desired selectivity effects can be replicated without using IPA.


3. Where IPA Is Useful

Despite its limitations, IPA has valuable niche applications in HPLC workflows:

  • Solvent bridging: IPA is miscible with both aqueous and non-aqueous solvents, making it ideal for transitioning between reversed-phase and normal-phase methods.
  • Column cleaning: IPA is effective at removing strongly retained hydrophobic contaminants. It can be used:
    • As a wash step at the end of a gradient
    • In dedicated column cleaning protocols, including backflushing


📦 Need help selecting the right solvent for your method? Our technical team is here to assist.

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