HPLC Troubleshooting
No peaks, baseline is absolutely flat
- The lamp in the detector is switched off or defective
- The connection cable between detector and control computer is not connected
- No flow of solvent
- Switch on or replace the lamp on the detector
- Check all cables and connections
- Check storage vessel, start pump(s)
No peaks, baseline shows slight noise.
- Wrong flow direction
- No, too little, wrong sample injected
- Wrong sensitivity / wavelength of the detector
- Set up and start pumps correctly
- Check samples or autosampler
- Check settings on the detector
Strong noise with regular peaks.
- Check pumps, possibly air bubbles in the valve on the pump head
- Use pulsation damper
Strong noise with long flat drift.
- Move the HPLC column into the column thermostat
- Protect the HPLC system from changing ambient temperatures
Strong noise with sharp negative spikes.
- Use shielded cables
- Use a power supply with galvanic isolation (UPS)
- Connect the complete HPLC system to a different circuit
Extremely strong noise.
- Rinse flow cell until air is removed
- Use a back pressure restrictor at the inlet of the flow cell
- Use a solvent filter and/or degas the solvent
Regular noise.
- The mixer is defective
- Defective lamp in the detector
- Eluent absorption too high
- Check mixer
- Replace lamp
- Change eluent / wavelength
Irregular noise.
No peaks and no back pressure, no flow at the detector.
- Pump(s) is/are switched off
- Air bubble in valve at pump head
- Leakage at connection or suction hose defective
- Supply vessel empty or suction hose not in running medium
- Check pump(s) and switch on
- Rinse pump head and tap lightly on valve
- Check / seal or renew connections
- Refill eluent, fasten suction hose
No peaks but high back pressure or alarm.
- Suction hose or filter clogged
- HPLC column or frit clogged
- Sample feed valve or sample loop clogged
- Capillary squeezed / plugged at port
- Remove blockage, clean filter in ultrasonic bath or replace.
- Rinse column and clean frit in ultrasonic bath or replace
- Disassemble and clean valve, rinse or replace loop
- Cut off damaged area of capillary and reconnect it
Slow pressure increase.
- Frit at column inlet or column clogged.
- Frit clogged in mixer.
- Use / replace pre-column, possibly counter-rinse column.
- Clean frit in ultrasonic bath or replace.
Sudden pressure increase.
- Defective or poorly switching valve.
- Sample has precipitated.
- Check and clean valves
- Rinse column or system
Pressure fluctuations.
- Air in the pump or in the suction line to the pump
- Leaky line between pump and column
- Degas the solvent or purge with helium.
- Tighten the screw connections of the lines.
Pressure drop.
- No flow of the mobile phase
- Leaky liquid line between pump and column
- Check the system for loose screw connections and eluent reservoirs.
- Systematically search for and eliminate leakage.
High pressure increase.
- Contaminates at the column inlet, precipitation of buffer salts.
- Viscosity of the mobile phase is too high
- Particles of the column material are too small
- Remove column and backwash with strong solvent. Replace clogged filter elements and pre-column. Does the solvent match the buffer concentration?
- Change solvent or increase column temperature.
- Use HPLC column with larger particles (e.g. 8 µm instead of 5 µm).
Tailing, blurred peaks at base, often with shifted retention time.
Fronting, without retention time shift.
- Dead volume between injector and column.
- HPLC column defective.
- Check injector / tubing for dead volume.
- Replace HPLC column.
Broad flat peaks with roof.
Doubling, all peaks have two maxima
- Channel formation in the column.
- Injector defective.
- Replace HPLC column.
- Check and repair injector.
Retention time shift in one direction.
- Leaking pump seal.
- Column overload.
- Column not equilibrated.
- Replace pump seals
- Inject lower sample concentration
- Equilibrate 2 to 3 column volumes
Arbitrary retention time shift.
- Temperature fluctuations of the column.
- Valve on pump head or proportioning valve defective
- Use column thermostat.
- Check / replace valves.
Peaks are significantly smaller than expected.
- Injection volume too low.
- Eluent with higher adsorption.
- Dirty flow cell in detector.
- Check injection volume.
- Use suitable (HPLC-grade) eluent.
- Rinse flow cell in detector.
Reproducible ghost peaks.
- Dirty injection valve.
- Peak from previous run.
- Injection with air.
- Rinse injection valve.
- Run previous run longer.
- Check injection volume.
Arbitrary ghost peaks.
- Sample solvent is contaminated.
- Air in flow cell in detector.
- HPLC column is dirty.
- Re-prepare sample.
- Rinse flow cell, use backpressure restrictor.
- Rinse or replace HPLC column.
Medium leaks at fitting.
- PEEK tubing: shorten to correct length and reassemble.
- Stainless steel tubing: detach tubing including the ferrule, remove burr and mount with new ferrule.
A slight shoulder forms at the first peak.
- Push the PEEK tubing to the maximum length into the loosened screw connection and tighten again.
- Stainless steel tubing: detach tubing including ferrule, remove burr and mount with new ferrule.