Troubleshooting Library
Chromatography Troubleshooting
Symptom-first guides for HPLC, UHPLC, GC and LC-MS — what the instrument is telling you, how to isolate the cause, and what to change. 133 articles, grouped by the part of the system at fault.
Pump & Pressure
19 articles- Air Entrapment in HPLC Pump Heads and Flow Instability
- Diagnosing HPLC Pump Leaks Using Pressure Isolation
- Flow Rate Inaccuracy in HPLC and Retention Time Variability
- Fluctuating HPLC Pressure from Faulty Pump Check Valves
- Gradient Proportioning Valve Malfunction in HPLC Pumps
- High HPLC System Pressure Caused by Pump Blockages
- How often should I replace check valves, seals, frits, and inline filters?
- Low or No HPLC Pressure Due to Pump Seal Failure
- Prime Valve Malfunctions and No-Flow Conditions in HPLC
- Pulse Dampener Failure and Baseline Oscillations in HPLC
- Pump Cavitation in HPLC: Causes, Symptoms, and Solutions
- Salt Crystallization at HPLC Pump Fittings and Flow Restriction
- Viscous Mobile Phases and Their Impact on HPLC Pump Performance
- What causes baseline drift in HPLC, especially during gradients?
- What causes cavitation or air in the pump, and how do I purge it correctly?
- What causes HPLC pressure to fluctuate or ripple?
- When to Replace HPLC Pump Pistons Versus Seals
- Why is my HPLC pressure suddenly high (high backpressure)?
- Why is system pressure high even when the purge valve is open?
Column & Guard Column
18 articles- Column Aging and Gradual Retention Time Drift in HPLC
- Column Compatibility with High-pH Mobile Phases in HPLC
- Column Overloading in HPLC and Resulting Peak Fronting
- Column Temperature Sensitivity in Ion-Exchange HPLC Methods
- Column Void Formation and Abnormal Peak Shapes in HPLC
- Diagnosing Column Problems Using HPLC Standard Test Mixtures
- Guard Column Blockage and Rising Backpressure in HPLC
- Guard Column Selection for Complex Sample Matrices
- How do I isolate whether a blockage is before or after the column?
- How do I tell whether the column is failing versus the system being contaminated?
- HPLC Column Cleaning Versus Replacement Decision Criteria
- HPLC Column Contamination and Loss of Chromatographic Resolution
- Improper Column Storage and Permanent HPLC Performance Loss
- Inlet Frit Blockage and Split Peaks in HPLC Columns
- Particle Size Effects on HPLC System Pressure
- Peak Tailing in HPLC Caused by Active Silanol Sites
- Phase Collapse in Reversed-Phase HPLC Columns
- Reversed-Phase vs Normal-Phase HPLC Column Failure Modes
Detector
41 articles- Air Bubbles in HPLC Detector Flow Cells
- Baseline Drift Caused by Detector Temperature Instability
- Detector Saturation and Nonlinear Response in HPLC
- Detector Settings and Data Acquisition Problems Affecting LC Sensitivity
- Detector Time Constant Effects on HPLC Peak Shape
- Detector Warm-Up Time and HPLC Data Reliability
- Differentiating Detector Faults from Chromatographic Problems
- Dirty HPLC Detector Flow Cells and Baseline Noise
- Electrical Noise vs Fluid Path Noise in HPLC Detectors
- Fluorescence Detector Quenching Effects in HPLC
- How do I recognize ion source contamination and what should I clean first?
- How do I troubleshoot unstable spray or nebulizer issues in ESI?
- HPLC Detector Lamp Aging and Loss of Sensitivity
- HPLC Detector Leaks and Seal Failures
- Incorrect Wavelength Selection Causing Missing HPLC Peaks
- Ion Suppression in LC-MS Caused by Mobile Phase Additives
- Is baseline noise caused by the pump or by the UV lamp or optics?
- Loss of Detector Response in Liquid Chromatography: Practical Troubleshooting Guide
- Low Sensitivity in HPLC and UHPLC: Causes, Diagnostics, and Corrective Actions
- Matrix Effects and Signal Suppression in LC-Based Methods: Identification and Mitigation
- Poor Signal Intensity in LC and LC-MS: System, Method, and Sample-Related Causes
- Pump-Related Baseline Noise in UV and RI Detectors
- Refractive Index Detector Sensitivity to Pressure Changes
- UV Baseline Spikes from External Electrical Interference
- UV-Vis Detector Flow Cell Backpressure Limits and Damage
- What are the most common causes of carryover and ghost peaks?
- What causes GC baseline drift and baseline problems over a run?
- What causes high background in LC-MS and reduced sensitivity?
- What causes negative peaks or baseline dips in HPLC?
- What causes retention time drift or unstable retention times?
- Why am I losing GC-MS signal over time when running dirty samples?
- Why are my peaks tailing, fronting, splitting, or broad?
- Why did my LC-MS signal suddenly drop or disappear?
- Why did my resolution suddenly drop even though the method is unchanged?
- Why does baseline drift worsen at low UV wavelengths with certain additives or solvents?
- Why does LC-MS autotune fail, and what should I check first?
- Why does my baseline shift after injection even when peaks still appear?
- Why does my chromatogram look clipped or poorly sampled due to data rate or time constant issues?
- Why does my instrument show a gradual loss of MS sensitivity over time?
- Why does reintegration change results so much, and how should I set integration?
- Why is my baseline noisy or wavy during blanks or long runs?
Mobile Phase & Solvent Delivery
15 articles- Air Bubbles in HPLC Solvent Lines: Symptoms, Detection, and Fixes
- Buffer pH Instability and Chromatographic Performance Issues in HPLC
- Buffer Precipitation in HPLC Systems: Causes, Prevention, and Cleanup
- Gradient Baseline Drift Caused by UV-Absorbing Mobile Phases
- Helium Sparging vs In-Line Degassing in HPLC Systems
- How do air bubbles and poor degassing affect pressure and baseline stability?
- How do I detect microbial growth or contamination in solvent bottles or lines?
- Improper Mobile Phase Preparation and Loss of HPLC Reproducibility
- Microbial Growth in Aqueous Mobile Phases and Its Impact on HPLC
- Mobile Phase Contamination in HPLC: Causes of Baseline Drift and Noise
- Mobile Phase Recycling Errors and Ghost Peak Formation in HPLC
- Poor Mobile Phase Degassing and Pressure Fluctuations in HPLC
- Solvent Evaporation Effects in Isocratic HPLC Methods
- Solvent Miscibility Problems and Retention Time Instability in HPLC
- Why does switching solvents cause new pressure fluctuations or baseline issues?
Injector & Autosampler
13 articles- Autosampler Carryover Caused by Inadequate Needle Washing
- Autosampler Prime Mode Errors and Injection Failures
- Blocked Autosampler Needles Causing Missing HPLC Peaks
- Injection Solvent Strength Mismatch and Peak Distortion in HPLC
- Injection Volume Limits in Isocratic and Gradient HPLC Methods
- Injector Leaks in HPLC and Associated Pressure Loss
- Injector Seal Wear and Progressive Peak Broadening in HPLC
- Manual vs Autosampler Injection Reproducibility in HPLC
- Overfilled Sample Vials and Vacuum Injection Failures in HPLC
- Sample Loop Underfilling and Variable Peak Areas in HPLC
- Septum Coring and Particulate Contamination in HPLC Systems
- Split HPLC Peaks Caused by Injection Solvent Effects
- Syringe Wear and Injection Volume Inaccuracy in HPLC
Tubing, Fittings & Filters
12 articles- Blocked In-Line Filters Causing Sudden HPLC Pressure Increases
- Dead Volume Effects on Early-Eluting Peaks in HPLC
- Detector Outlet Restrictions and Artificial Backpressure in HPLC
- Diagnosing HPLC Flow Restrictions by Sequential Isolation
- Flow Path Contamination After HPLC Method Changes
- HPLC Leaks at Fittings: Catastrophic vs Non-Catastrophic Failures
- Improper Swaging Techniques and Persistent HPLC Micro-Leaks
- Incorrect Tubing Inner Diameter and Extra-Column Band Broadening
- PEEK vs Stainless Steel Tubing in HPLC Flow Paths
- Salt Buildup at HPLC Connections and Flow Restriction
- Sample Particulates and Downstream Flow Path Damage in HPLC
- UHPLC Overpressure Caused by Improper Fitting Selection
System-Level
15 articles- Chromatographic Changes After Routine HPLC Maintenance
- Daily HPLC Pump Maintenance to Prevent Long-Term Failures
- Distinguishing Sample Preparation Errors from HPLC Instrument Problems
- Ghost Peaks and Carryover Diagnosis in HPLC
- HPLC Method Transfer Issues Between Instruments
- HPLC Troubleshooting Strategy: 5-Step Method to Diagnose and Fix Problems
- Importance of Instrument Logs in HPLC Troubleshooting
- Interpreting Baseline Noise Patterns in HPLC
- Loss of Sensitivity Across Multiple HPLC Samples
- No Peaks Detected in HPLC: A Systematic Troubleshooting Workflow
- Poor Quantitative Reproducibility in HPLC Systems
- Systematic HPLC Troubleshooting Process: Facts, Simple Checks, and One-Change Testing
- Using HPLC Pressure Profiles as Diagnostic Tools
- Variable Retention Times Across HPLC Runs
- What routine maintenance prevents pressure fluctuations and retention instability?