Essential Guides to Method Development in Solid-phase Extraction

Poor peak shape Wrong silica type Use type B silica Blocked frit or column void Replace frit, backflush column Silanol interactions Use amine additives, change pH, use end-capped stationary phase Excessive peak width Bad column Replace column Column overload Reduce injection volume or mass High molecular weight Normal Unresolved peaks Improve separation Inadequate retention Mobile phase too strong Use lower %B Column too weak Switch to C18 Samples ionized Change pH Samples too polar Change to normal phase Gradient starting too strong Start at lower %B Excessive retention Mobile phase too weak Use higher %B Column too retentive Switch to C8, C4 or CN Samples too hydrophobic Change to normal phase Gradient stops too soon Stop at higher %B Excessive retention range Acids and bases or bases and neutrals in sample Use ion pairing Too broad of polarity for isocratic method Use gradient elution Inadequate resolution Retention too short Increase k Poor selectivity Change Plate number too low Use longer column or smaller particle size