Identifying mixture components is a well-known challenge in analytical chemistry. The Inverted Library Search Algorithm is a recently proposed method for identifying mixture components using in-source collision induced dissociation (is-CID) mass spectra of a query mixture and a reference library of pure compound is-CID mass spectra (J. Am. Soc. Mass Spectrom.20213217251734). This article presents several subtle but important advances to the algorithm, including updated compound matching strategies that improve result explainability and spectral filtering to better handle noisy mass spectra as is often observed with real-world samples such as seized drug evidence.

Chromatographic-less mass spectrometry techniques like direct analysis in real time mass spectrometry (DART-MS) are steadily being employed as seized drug screening tools.However, these newer analytical platforms require new computational methods to best make-use of the collected data. The inverted library search algorithm (ILSA) is a recently developed method designed specifically for working with mass spectra of mixtures collected with DART-MS, and has been implemented as a function in the NIST/NIJ DART-MS Data Interpretation Tool (DIT). This paper demonstrates how DART-MS and the ILSA/DIT can be used to analyze seized drug evidence, while discussing insights gathered during the evaluation of several adjudicated case samples. The evaluation verified that the combination of DART-MS and the ILSA/DIT can be used as an informative tool to help analysts screen seized drug evidence, but also revealed several factors an analyst must consider while employing these methods-all of these considerations are summarized in this paper.