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What are common causes of low resolution for a liquid chromatography (LC) column? - WKB244143

Article number: 244143

ENVIRONMENT

  • Column performance
  • Low resolution
  • Wide peaks
  • Matrix

ANSWER

Common causes of low resolution include (but are not limited to):

  1. System dispersion (band spread, band broadening) is too high.
    • Too much system volume between the injector and the detector leads to wider peaks and, sometimes, tailing.
      • New flow cell that has more volume than the old flow cell
      • New tubing that has more volume than the old tubing
  2. Poor connections in the flow path between the injector and the detector:
    • Incorrect (too short) ferrule depth can cause voids inside the end fitting.
      • Make a new connection.
    • Slipped ferrule (tubing can slip inside the end fitting, causing a void)
      • Can occur when using PEEK finger-tight fittings.
      • Install a new fitting.
  3. Non-specific binding:
    • Proteins and acidic analytes can adsorb to stainless steel surfaces (through cationic attraction) and to the particles, as well through hydrophobic or hydrophilic attraction (depending on particle type):  
      • Make several "conditioning injections" with a high concentration of the analyte to saturate "active sites" on the stainless steel and particle surfaces to improve recovery and resolution.
  4. Matrix component buildup on the column:
    • Sample matrix may foul columns, building up on the column injection to injection.
      • Perform column cleaning procedure.
  5. Microbial growth/contamination:
    • May cause peak tailing but more often causes split peaks, lower resolution, and high-pressure problems
      • Replace high-aqueous mobile phases every 24-48 hours if possible when running 2.5-µm and sub-2µm particle columns.
  6. System problems (including but not limited to):
    • Incorrect flow rate being delivered by the system
    • Incorrect column temperature
    • Incorrect solvent mix

ADDITIONAL INFORMATION

Waters now offers MaxPeak Premier columns, which prevent acidic analytes from adsorbing to the stainless steel surfaces inside the columns.

See: MaxPeak Premier Columns Web Page

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