Multiple Ion Transition Summation of Isotopologues for Improved Mass Spectrometric Detection of N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine.

Multiple ion transition summation of isotopologues (MITSI) is an adaptable and easy-to-implement methodology for improving analytical sensitivity, especially for halogenated compounds and otherwise abundant isotopologues. This novel application of signal summing was applied to measure and quantitate the two most abundant ion transitions of two isotopologues of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (1DCV), a urinary metabolite of trichloroethylene (TCE). Because 1DCV is dichlorinated, only approximately half of the total potential signal is quantifiable when the monoisotopic ion transition (i.e., m/z 256 → 127 for 35Cl2) is monitored. By summing the intensity of a separate and high-abundance 1DCV isotopologue ion transition (i.e., m/z 258 → 129 to include 35Cl and 37Cl), overall signal intensity increased by over 70%. This summation technique improved the analytical sensitivity and limit of detection (LOD) by factors of 2.3 and 2.9, respectively, compared to monitoring the two transitions separately, without summation. Separation and detection were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in negative-ion mode with scheduled selected reaction monitoring. This approach was verified for accuracy and precision using two quality control materials. In addition, we derived a modified signal summation equation to calculate predicted signal enhancements specific to the MITSI approach. Graphical Abstract .