Three easy ways to minimize chromatography peak tailing:
(1) Tailing often results from using “Type – A” HPLC silica. Type-A silica often contains
more acidic silanol groups and metal impurities than Type-B. To improve peak shape, use modern “Type – B” silicas which
are of higher overall purity, have less metal contamination and feature minimal silanol ionization under higher pH
conditions.
(2) Minimize ionic interactions and utilize a buffer or ion
pairing agent (e.g. TFA 0.02%) in your mobile phase. Select a buffer that is at least 2.0 pH units away from your sample's pKa and use the smallest concentration or amount that gets the job done. For LC/MS or MS/MS applications, remember to only use volatile buffers and avoid the use of ion pairing agents unless absolutely necessary (and if used, use at the lowest possible concentration to avoid source contamination).
(3) Always use a freshly washed and equilibrated column. Is the column fouled or the inlet frit dirty? If the head of the
column is fouled from sample overloading or from a failure to wash off strongly retained
compounds from many runs (much more common problem), then your peak shape and reproducibility will suffer. Incorporate a washing step in
between your analysis methods which utilizes a solvent which is stronger
(in concentration) than your mobile phase to wash off any strongly
retained material after each run. For example, if you normally end a method with an 80% concentration of ACN, utilize a separate wash method which has 95% ACN in it. Allow enough wash time for this work.
