Isotopic pattern and accurate mass determination in urine drug screening by liquid chromatography/time-of-flight mass spectrometry

An efficient method was developed for toxicological drug screening in urine by liquid chromatography coupled with electrospray ionization time‐of‐flight mass spectrometry. The method relies on a large target database of exact monoisotopic masses representing the elemental formulae of reference drugs and their metabolites. Mass spectral identification is based on matching measured accurate mass and isotopic pattern (SigmaFit™) of a sample component with those in the database. Data post‐processing software was developed for automated reporting of findings in an easily interpretable form. The mean and median of SigmaFit™ for true‐positive findings were 0.0066 and 0.0051, respectively. The mean and median of mass error absolute values for true‐positive findings were 2.51 and 2.17 ppm, respectively, corresponding to 0.65 and 0.60 mTh. For routine screening practice, a SigmaFit™ tolerance of 0.03 and a mass tolerance of 10 ppm were chosen. Ion abundance differences from urine extracts did not affect the accuracy of the automatically acquired SigmaFit™ or mass values. The results show that isotopic pattern matching by SigmaFit™ is a powerful means of identification in addition to accurate mass measurement. Copyright © 2006 John Wiley & Sons, Ltd.