Dilute-and-shoot-liquid chromatography-mass spectrometry for urine analysis in doping control and analytical toxicology

Abstract In the past 20 years, liquid chromatography-mass spectrometry (LC-MS) has become a standard analytical technique in doping control and toxicology laboratories. Research groups have successfully applied it to detect substances by direct injection, or “dilute-and-shoot”-LC-MS (DS-LC-MS). However, some urinary components can precipitate into the vial, hampering the correct injection. Dissolved urinary matrix is responsible for shifted retention times and ion suppression or ion enhancement. To compensate for the effect of the matrix, an isotope-labeled internal standard (IL-ISTD) is the best choice. Dilution can also minimize the matrix effect, but can result in reduced analyte detectability. Hence, DS-LC-MS methods are predominantly available for substances for which the required urinary detection levels are high and that show good ionization efficiency. Taking into account the progressive increase in instrument sensitivity, we expect that the application of DS-LC-MS will also come available for substances with low required detection levels or limited ionization efficiency.