Gas chromatography-mass spectrometry (GC-MS) is a firstchoice approach for the measurement of small molecule metabo-lites and in particular of primary metabolites such as organic acidsand amino acids in clinical settings [1]. This preference stemsfrom the significant advantages offered by GC-MS, such as theexistence of commercial spectral libraries, the potential for directcomparison and exchange of results from different laboratories,the unchallenged chromatographic resolution and the accumulatedexperience in the field. Despite recent developments in liquid chro-matography (LC), such as the advent of HILIC or other LC modesthat show good retention of polar compounds, LC-MS/MS analy-sis of small molecule acids remains a challenge. In toxicity studiesdetection sensitivity is not an issue, so GC-MS is often preferred toLC-MS/MS; on the other hand, LC-MS/MS is dominating the analysisof long fatty acids and bile acids [2]. A potential problem howeverwith GC-MS is the need for derivatization for numerous analytesincluding organic acids.