Matrix effects are also compound dependent. Bonfiglioet al. [24] reported that the chemical nature of a compoundhas a significant effect on the degree of matrix effects. In astudy of four compounds of different polarities under thesame mass spectrometric conditions, the most polar wasfound to have the largest ion suppression and the least polarwas affected less by ion suppression. These findings ofdifferential matrix effects have important ramificationsparticularly when selecting a suitable internal standard forquantification purposes. For example, if a drug and aglucuronide metabolite were quantified by internal standardizationagainst a close analogue of the parent drug andmatrix effects were slightly different between samples, thenthe change in ionization of the more polar glucuronidemetabolite would probably not be compensated by theinternal standard. Thus if there are multiple analytes to bequantified, with varying degrees of polarity, there may berequirements for multiple internal standards [25]