These calibrants offer great versatility because the components can be specifically chosen to satisfy the particular requirements of an analysis. For low resolution studies a mixture with quite broad ion-mass spacing can be used and for high resolution mass analysis an acid can be chosen that produces cluster ions that bracket the analyte ion of interest. Assignment of the calibrant mass spectrum is straight forward especially for monobasic acid / NaOH mixtures where the ions will have the following general formulas: Nan(acid anion)n+1 for negative ion and Nan(acid cation)n-1 for positive ions. For dibasic acids the situation is complicated by the tendency of these compounds to aggregate into dimers (without metal ions) but the task of mass assignment is still not difficult.
Advantages of this approach are numerous. The concentration of the calibrant components is usually quite low (micromolar) and it is always possible to formulate a mixture with the right ion spacing for the particular analysis. The same mixture at the same concentration can often be used as a calibrant in both positive and negative ion modes. Awareness of the tendency for salts to form clusters can allow internal calibration where salts are already present in the solution with the analyte (eg direct analysis of HPLC fractions which have acetic acid in the mobile phase). The materials needed are inexpensive and readily accessible.
Disadvantages are few and relate mainly to internal calibration where the relative amounts of calibrant and analyte have to be adjusted so ionisation of one is not completely suppressed by the other - a common theme in most internal calibrant strategies.