Characterization of drug interferences caused by coelution of substances in gas chromatography/mass spectrometry confirmation of targeted drugs in full-scan and selected-ion monitoring modes.

Interference by substances coeluting with targeted drugs is a general problem for gas chromatographic/mass spectrometric analysis of urine. To characterize these interferences, we examined human urine samples containing benzoylecgonine and fluconazole, and other drug combinations including deuterated internal standards that coelute (ISd,c) with target drugs, by selected-ion monitoring (SIM) and full-scan mass spectrometry. We show that, by SIM analysis, detecting the presence of an interferent is dependent on the specific IS used for the assay. When an ISd,c is used, the presence of another coeluting substance (interferent) suggests that the intensity of IS ions is substantially diminished, because the interferent affects both the ISd,c and target drug. When a noncoeluting IS (ISnc) is used, the interferent cannot be discerned unless it coincidently contains one or more of the ions monitored for either the target drug or ISnc. Under full-scan analysis, a coeluting interferent is directly discernable by examining the total ion gas chromatogram.