Problem	Potential cause	Solution
Poor quality LC-MS run	Problem with Sample or with HPLC column	Run a peptide standard; if standard = poor, replace HPLC if standard = fine, problem with sample
Poor electrospray stability or overall low signal intensity	Insufficient desalting	More washes of sample during peptide recovery
Sudden increase in HPLC pressure	Particulate debris in the sample	Replace HPLC column, lines, junctions to autosampler, and/or the rotor and stator of the autosampler valve; Centrifuge peptide sample at 16000 x g, transfer top 90% of volume
Poor chromatography – fronting peaks (peak skews to earlier retention time)	Column capacity overloaded due to overly concentrated peptide sample	Dilute sample
Poor chromatography – tailing peaks (peak skews to later retention time)	Residual reactive silanol groups in the stationary phase, or improper formulation of the mobile phases (pH)	Replace HPLC column and/or HPLC buffers