Cysteine-S-sulfate (SSC) is produced by reaction of inorganic sulfite and cystine by a as-yet-unknown pathway, and is a very potent NMDA-receptor antagonist. Cysteine-S-sulfate is a very polar molecule with one basic group, one carboxylic group and one sulfate group. It is retained by Primesep SB column by combination of strong anion-exchange mechanism and weak reversed-phase mechanism. Compound can be monitored by LC/MS, ELSD, Corona or UV detectors. This HPLC method can be adopted as generic approach for analysis of acidic and hydrophobic drugs.