A fast, semi-automated calibration system for the quantification of trace elements by inductively coupled plasma mass spectrometry (ICP-MS) was developed. A gradient based system was used, which offers the possibility of complete multi-element calibration within 10 min. For validation of this fast gradient calibration system (FGC) trace elements have been quantified in certified reference materials. The calibration principle and comparison with external calibration is presented. Due to the significance of hyphenated techniques, the usability of the FGC method to such systems is demonstrated by automated FGC coupled to size-exclusion chromatography (SEC). This system was used for determination of trace elements in biological samples and validated by analysis of certified human blood.