Common Causes of Pressure Drop in HPLC

1. Mobile phase issues: Bubbles in the mobile phase may arise from insufficient conventional ultrasonic degassing, sudden temperature rise causing solvent gas evolution, or prolonged storage leading to microbial growth, all of which can result in low pressure and pressure fluctuations.

Solvent filter clogging or insufficient mobile phase: Prolonged non-replacement of solvent filters may lead to impurity accumulation, while inadequate immersion of the tubing in the mobile phase bottle or tubing aging with cracks causing air ingress can similarly result in insufficient liquid suction by the pump and pressure drop.

Changes in the flow ratio or composition: During gradient elution, faults in the proportion valve, uneven mixing of the mobile phase when manually mixed, or volatilization of mobile phase components (e.g., volatile solvents such as methanol and acetonitrile) can all lead to deviations in the actual mobile phase ratio from the set value, resulting in abnormal pressure reduction.

2. Pump system issues: Check for blocked or damaged check valves. Residual sample impurities or crystallization of the mobile phase (e.g., due to inadequate flushing of buffer salt solution) may cause valve core jamming, preventing proper closure and resulting in insufficient pump output pressure.

Seal ring aging or wear: Prolonged use leads to reduced elasticity of the seal ring, resulting in leakage. This not only decreases pressure but may also contaminate the mobile phase, thereby affecting experimental results.

Air bubbles in the pump head: Incomplete exhaust of the pump head, insufficient degassing of the mobile phase, or failure to evacuate air from the pump head promptly during mobile phase replacement can all lead to unstable and low pump output pressure.

3. Pipeline connection issues: Loose joints or leakage: Prolonged disassembly of joints may lead to wear, loss of sealing rings, or improper tightening during connection, resulting in leakage of the mobile phase and pressure drop. Severe leakage may also contaminate the laboratory environment.

Pipeline blockage or dead volume: Partial blockage may result from pipeline bending, residual sample impurities on the inner wall, or improper pipeline connections leading to dead volume, which obstructs the smooth passage of the mobile phase, causing localized pressure abnormalities and manifesting as overall system pressure reduction.