Chromatography Troubleshooting List

Learn the most common causes of sudden high HPLC backpressure and how to systematically isolate column, tubing, and pump-related restrictions.

Understand why HPLC pressure can remain high with the purge valve open and how to determine whether the issue is mechanical or downstream.

Explore the primary reasons for fluctuating or rippling HPLC pressure, including pump performance, air entrainment, and mobile phase effects.

This guide explains step-by-step methods to locate HPLC blockages upstream or downstream of the column without damaging the system.

Learn how pump cavitation occurs in HPLC systems and the correct procedures to remove trapped air and restore stable flow.

Understand the chemical and instrumental factors that cause baseline drift in gradient HPLC, including solvent absorbance and temperature effects.

Identify the most common sources of HPLC baseline noise during blanks or extended runs and how to distinguish pump noise from detector issues.

This article explains how to differentiate pump-related noise from UV detector or optical instability in HPLC systems.

Learn why negative peaks or baseline dips occur in HPLC and how solvent mismatch and detector settings contribute to the problem.

Explore why baseline offsets occur after injection in HPLC and how injection solvent composition and system equilibration affect results.

This guide explains the most frequent causes of poor HPLC peak shape related to column condition, chemistry, and injection technique.

Understand why chromatographic resolution can decline unexpectedly due to column aging, system dispersion, or mobile phase changes.

Learn the key factors that cause retention time drift in HPLC, including temperature variation, mobile phase composition, and system equilibration.

This article reviews typical sources of HPLC carryover and ghost peaks and how to eliminate them through cleaning and method optimization.

Understand how dissolved gases and air bubbles disrupt HPLC pressure stability and baseline performance.

Learn why changing solvent type or brand can impact HPLC pressure and baseline behavior even when methods remain unchanged.

This guide explains how to identify microbial contamination in HPLC solvents and tubing and how to prevent future growth.

Explore why baseline drift increases at low UV wavelengths and how solvent absorbance and additives influence detector response.

Understand the most common causes of sudden LC-MS signal loss, including ion source contamination, tuning issues, and spray instability.

Learn why LC-MS sensitivity often declines gradually due to contamination, wear, or matrix buildup and how to restore performance.

This article explains how background ions, contamination, and mobile phase impurities reduce LC-MS sensitivity.

Learn how to identify ion source contamination in LC-MS systems and which components should be cleaned first.

Understand the most common reasons LC-MS autotune routines fail and the critical system checks to perform before retuning.

This guide explains how to diagnose unstable electrospray ionization caused by flow, gas, or solvent-related problems.

Learn how improper acquisition rate or time constant settings distort chromatographic peak shape and quantitative accuracy.

Understand why reintegration alters quantitative results and how to set integration parameters consistently and correctly.

This article outlines typical replacement intervals for critical HPLC components to maintain pressure stability and performance.

Learn which routine HPLC maintenance tasks are most effective for preventing pressure and retention time instability.

This guide explains how to distinguish column degradation from system contamination using diagnostic tests and observations.

Understand the most common causes of GC baseline drift, including column bleed, detector issues, and temperature programming.

Learn why GC-MS signal degrades when analyzing dirty samples and how contamination affects ion source and detector performance.

Troubleshoot Mobile Phase Contamination in HPLC: Causes of Baseline Drift and Noise: isolation steps and corrective actions to eliminate spikes and waviness.

Learn how to troubleshoot Poor Mobile Phase Degassing and Pressure Fluctuations in HPLC: root causes, diagnostic checks, and fixes to stabilize system pressure.

Quick diagnostic guide for Air Bubbles in HPLC Solvent Lines: Symptoms, Detection, and Fixes: checks, likely causes, and corrective actions to recover sensitivity.

Troubleshoot Solvent Miscibility Problems and Retention Time Instability in HPLC: checks, likely causes, and corrective actions to stop run-to-run drift.

Learn how to troubleshoot Buffer Precipitation in HPLC Systems: Causes, Prevention, and Cleanup: common causes and practical remedies to recover sensitivity.

Quick diagnostic guide for Microbial Growth in Aqueous Mobile Phases and Its Impact on HPLC: root causes, diagnostic checks, and fixes to improve peak shape and resolution.

Quick diagnostic guide for Gradient Baseline Drift Caused by UV-Absorbing Mobile Phases: what to check first and how to correct it to eliminate spikes and waviness.

Technical guide to troubleshoot Solvent Evaporation Effects in Isocratic HPLC Methods: symptoms, tests, and proven corrections to reduce pressure spikes.

Field guide to troubleshoot Helium Sparging vs In-Line Degassing in HPLC Systems: symptoms, tests, and proven corrections to restore stable baselines.

Learn how to troubleshoot Improper Mobile Phase Preparation and Loss of HPLC Reproducibility: symptoms, tests, and proven corrections to prevent downtime.

Field guide to troubleshoot Mobile Phase Recycling Errors and Ghost Peak Formation in HPLC: checks, likely causes, and corrective actions to improve peak shape.

Technical guide to troubleshoot Buffer pH Instability and Chromatographic Performance Issues in HPLC: symptoms, tests, and proven corrections to improve reproducibility.

Diagnose Gradient Proportioning Valve Malfunction in HPLC Pumps: common causes and practical remedies to recover sensitivity.

How to resolve Daily HPLC Pump Maintenance to Prevent Long-Term Failures: what to check first and how to correct it to reduce pressure spikes.

Quick diagnostic guide for Diagnosing HPLC Pump Leaks Using Pressure Isolation: root causes, diagnostic checks, and fixes to stabilize system pressure.

Learn how to troubleshoot Viscous Mobile Phases and Their Impact on HPLC Pump Performance: checks, likely causes, and corrective actions to improve reproducibility.

Step-by-step guide to fix When to Replace HPLC Pump Pistons Versus Seals: checks, likely causes, and corrective actions to improve reproducibility.

Practical guide to diagnose Prime Valve Malfunctions and No-Flow Conditions in HPLC: root causes, diagnostic checks, and fixes to reduce pressure spikes.

Field guide to troubleshoot Pump-Related Baseline Noise in UV and RI Detectors: isolation steps and corrective actions to eliminate spikes and waviness.

Step-by-step guide to fix Sample Loop Underfilling and Variable Peak Areas in HPLC: root causes, diagnostic checks, and fixes to recover resolution.

Quick diagnostic guide for Injector Leaks in HPLC and Associated Pressure Loss: common causes and practical remedies to restore normal pressure.

Technical guide to troubleshoot Blocked Autosampler Needles Causing Missing HPLC Peaks: what to check first and how to correct it to recover resolution.

Practical guide to diagnose Injection Solvent Strength Mismatch and Peak Distortion in HPLC: root causes, diagnostic checks, and fixes to fix split or tailing peaks.

How to resolve Autosampler Carryover Caused by Inadequate Needle Washing: checks, likely causes, and corrective actions to reduce carryover.

Diagnose Split HPLC Peaks Caused by Injection Solvent Effects: isolation steps and corrective actions to improve peak shape.

Field guide to troubleshoot Septum Coring and Particulate Contamination in HPLC Systems: common causes and practical remedies to stabilize retention times.

Field guide to troubleshoot Autosampler Prime Mode Errors and Injection Failures: common causes and practical remedies to recover sensitivity.

Step-by-step guide to fix Syringe Wear and Injection Volume Inaccuracy in HPLC: common causes and practical remedies to minimize carryover.

Fix Overfilled Sample Vials and Vacuum Injection Failures in HPLC: isolation steps and corrective actions to restore stable baselines.

Practical guide to diagnose Manual vs Autosampler Injection Reproducibility in HPLC: checks, likely causes, and corrective actions to reduce noise and drift.

Diagnose Injector Seal Wear and Progressive Peak Broadening in HPLC: what to check first and how to correct it to recover resolution.

Step-by-step guide to fix Injection Volume Limits in Isocratic and Gradient HPLC Methods: common causes and practical remedies to restore stable baselines.

Fix Blocked In-Line Filters Causing Sudden HPLC Pressure Increases: isolation steps and corrective actions to restore normal pressure.

Quick diagnostic guide for Incorrect Tubing Inner Diameter and Extra-Column Band Broadening: common causes and practical remedies to recover resolution.

Practical guide to diagnose HPLC Leaks at Fittings: Catastrophic vs Non-Catastrophic Failures: root causes, diagnostic checks, and fixes to stop leaks quickly.

Troubleshoot Salt Buildup at HPLC Connections and Flow Restriction: common causes and practical remedies to reduce noise and drift.

Troubleshoot Improper Swaging Techniques and Persistent HPLC Micro-Leaks: checks, likely causes, and corrective actions to prevent solvent loss and damage.

Learn how to troubleshoot Detector Outlet Restrictions and Artificial Backpressure in HPLC: checks, likely causes, and corrective actions to stabilize system pressure.

Fix Sample Particulates and Downstream Flow Path Damage in HPLC: checks, likely causes, and corrective actions to reduce pressure spikes.

Fix UHPLC Overpressure Caused by Improper Fitting Selection: common causes and practical remedies to prevent pressure-related shutdowns.

How to resolve PEEK vs Stainless Steel Tubing in HPLC Flow Paths: common causes and practical remedies to stabilize retention times.

Quick diagnostic guide for Flow Path Contamination After HPLC Method Changes: common causes and practical remedies to stabilize retention times.

Quick diagnostic guide for Dead Volume Effects on Early-Eluting Peaks in HPLC: isolation steps and corrective actions to recover resolution.

Step-by-step guide to fix Diagnosing HPLC Flow Restrictions by Sequential Isolation: what to check first and how to correct it to reduce pressure spikes.

Practical guide to diagnose Guard Column Blockage and Rising Backpressure in HPLC: what to check first and how to correct it to prevent pressure-related shutdowns.

Fix HPLC Column Contamination and Loss of Chromatographic Resolution: root causes, diagnostic checks, and fixes to reduce noise and drift.

Practical guide to diagnose Column Overloading in HPLC and Resulting Peak Fronting: checks, likely causes, and corrective actions to improve peak shape.

Learn how to troubleshoot Peak Tailing in HPLC Caused by Active Silanol Sites: common causes and practical remedies to fix split or tailing peaks.

Fix Phase Collapse in Reversed-Phase HPLC Columns: isolation steps and corrective actions to reduce pressure spikes. Includes quick checks and prevention tips.

Learn how to troubleshoot Column Aging and Gradual Retention Time Drift in HPLC: checks, likely causes, and corrective actions to eliminate spikes and waviness.

Fix Inlet Frit Blockage and Split Peaks in HPLC Columns: common causes and practical remedies to improve peak shape. Includes quick checks and prevention tips.

How to resolve Column Void Formation and Abnormal Peak Shapes in HPLC: root causes, diagnostic checks, and fixes to improve peak shape.

Technical guide to troubleshoot Particle Size Effects on HPLC System Pressure: common causes and practical remedies to prevent pressure-related shutdowns.

How to resolve Column Temperature Sensitivity in Ion-Exchange HPLC Methods: what to check first and how to correct it to increase signal-to-noise.

Fix HPLC Column Cleaning Versus Replacement Decision Criteria: isolation steps and corrective actions to reduce pressure spikes.

Field guide to troubleshoot Column Compatibility with High-pH Mobile Phases in HPLC: what to check first and how to correct it to protect columns and seals.

Troubleshoot Guard Column Selection for Complex Sample Matrices: isolation steps and corrective actions to minimize carryover.

Field guide to troubleshoot Reversed-Phase vs Normal-Phase HPLC Column Failure Modes: isolation steps and corrective actions to recover sensitivity.

Learn how to troubleshoot Improper Column Storage and Permanent HPLC Performance Loss: root causes, diagnostic checks, and fixes to improve reproducibility.

How to resolve Diagnosing Column Problems Using HPLC Standard Test Mixtures: root causes, diagnostic checks, and fixes to reduce pressure spikes.

Step-by-step guide to fix HPLC Detector Lamp Aging and Loss of Sensitivity: what to check first and how to correct it to increase signal-to-noise.

How to resolve Dirty HPLC Detector Flow Cells and Baseline Noise: common causes and practical remedies to reduce baseline noise.

Quick diagnostic guide for Incorrect Wavelength Selection Causing Missing HPLC Peaks: checks, likely causes, and corrective actions to improve peak shape.

Diagnose Detector Time Constant Effects on HPLC Peak Shape: what to check first and how to correct it to improve peak shape.

Learn how to troubleshoot Air Bubbles in HPLC Detector Flow Cells: what to check first and how to correct it to minimize carryover.

Field guide to troubleshoot Electrical Noise vs Fluid Path Noise in HPLC Detectors: checks, likely causes, and corrective actions to reduce baseline noise.

How to resolve Baseline Drift Caused by Detector Temperature Instability: symptoms, tests, and proven corrections to stop baseline drift.

Quick diagnostic guide for Refractive Index Detector Sensitivity to Pressure Changes: isolation steps and corrective actions to stabilize system pressure.

Learn how to troubleshoot Fluorescence Detector Quenching Effects in HPLC: symptoms, tests, and proven corrections to minimize carryover.