Simultaneous screening for 238 drugs in blood by liquid chromatography–ionspray tandem mass spectrometry with multiple-reaction monitoring

A liquid chromatography–tandem mass spectrometry (LC–MS–MS) method is presented for the qualitative screening for 238 drugs in blood samples, which is considerably more than in previous methods. After a two-step liquid–liquid extraction and C18 chromatography, the compounds were introduced into a triple quadrupole mass spectrometer equipped with a turbo ion spray ion source operating in the positive ionization mode. Identification was based on the compound’s absolute retention time, protonated molecular ion, and one representative fragment ion obtained by multiple reaction monitoring (MRM) at an individually selected collision energy of 20, 35, or 50 eV. The limit of detection (LOD) for the majority of the compounds (80%) was ≤0.05 mg/l, ranging from 0.002 mg/l (e.g., antihistamines) to 5 mg/l (acidic compounds), and for malathion it was 10 mg/l. The LOD values were sufficiently low to allow the majority of compounds to be detected at therapeutic concentrations in the blood.