An inventive substrate is provided which includes a substrate compound of formula A-B.sup.1--B.sup.2--B.sup.3: wherein A is a sugar moiety; B.sup.1 is a linker moiety allowing the conjugation of moiety A and the remaining structure of the substrate; B.sup.2 contains a permanently charged element such as a quaternary ammonium group so as to increase proton affinities and ionization efficiencies for mass spectrometry detection efficiencies analysis; and B.sup.3 of various carbon length conferring specificities to targeted enzymes. Also provided is a process to detect lysosomal diseases by contacting a sample with the inventive substrate along with an internal standard which is isotope-labeled analog of the product cleaved by a targeted enzyme upon the substrate.