| Column blocked wth irreversibly adorbed sample | Improve sample cleanup; use guard column; reverse-flush column with strong solvent to dissolve blockage |
| Column particle size too small (for example 3 micrometers) | Use larger particle size (for example 5 micrometer) |
| Microbial growth on column | Use at least 10% organic modifier in mobile phase; use fresh buffer daily; add 0.02% sodium azide to aqueous mobile phase; store column in at least 25% organic solvent without buffer |
| Mobile phase viscosity too high | Use lower viscosity solvents or higher temperature |
| Plugged frit in in-line filter or guard column | Replace frit or guard column |
| Plugged inlet frit | Replace endfitting or frit assembly |
| Polymetric columns - solvent change causes swelling of packing | Use correct solvent with column; change to proper solvent compositionl consult manufacturer's solvent-compatibility chartl use a column with a higher percentage of cross-linking |
| Salt precipitation (especially in reversed-phase chromatography with high concentration of organic solvent in mobile phase) | Ensure mobile phase compatibility with buffer concentration; decrease ionic strength and water-organic solvent ratio; premix mobile phase |
| When injector disconnected from column - blockage in injector | Clean injector or replace rotor |