Perchlorate contamination in drinking water may have different sources. Besides natural deposits, anthropogenic sources like fertilizers and rocket fuel residue add to hazardous water contamination. Perchlorate interferes with iodine uptake into the thyroid gland. Newborns and children are particularly vulnerable, affected as thyroid hormones are essential for growth. Besides ion chromatography (IC) followed conductivity detection, IC hyphenated with an MS detector can be used to measure perchlorate down to sub-µg/L levels. In this application IC is hyphenated with a triple-quadrupole MS (IC-MS/MS) for perchlorate determination in order to meet the requirements of EPA 332.0. This IC-MS/MS setup avoids the possible interference of sulfate.