Methodology is presented which greatly improves the sensitivity of ganglioside analysis by CE/MS without compromising separation efficiency In this method, non-volatile additives were removed, where possible, to reduce ion suppression Specifically, alpha-CD, used to break up ganglioside micelle formation, was replaced with isopropyl alcohol To reduce ion suppression from sodium ions, ammonium borate was substituted for sodium borate in the preparation of borate buffer Because borate anions were found to be essential for CE separation, a liquid-junction/low-flow interface was employed to restrict borate anions from entering the ESI ion source. With proper control over the EOF in the connecting capillary, borate anions were controlled to migrate away from the ESI ion source With these modifications, the sensitivity of CE/MS analysis of ganghosides was improved significantly.