To generate two major LC-HRMS semi-targeted screening libraries in addition to the in-house targeted library: (1) an extended general toxicology library by synchronizing an in-house targeted library with compounds found in Baselt's 12th Edition of Disposition of Toxic Drugs and Chemicals in Man, and (2) the extended general toxicology library synchronized with HighResNPS, a comprehensive database of NPS.

Firstly, InChiKeys for the compounds (n=1765) in the Waters Forensic Toxicology Screening Library (i.e. the targeted Library) were extracted in addition to the observed retention times and product ions. Secondly, compounds listed in Baselt (n=2057) were extracted from the contents and then converted to simplified molecular-input line-entry system (SMILES) strings and InChIKeys using Python's cheminformatics package, rdkit. Compounds which were not suited for LC-ESI-MS analysis, such as volatiles and elements, and compounds with masses either less than 50Da or greater than 1,000Da were removed. The precursor ion masses of the remaining compounds were calculated from the SMILES string. Lastly, the January 2022 library was downloaded from HighResNPS (n=2166), which contained InChIKeys and, both observed (n=351) and predicted (n=1815) retention times. Using the connectivity layer of the InChIKey, i.e. the first 14 characters, the target library and the Baselt library were combined so that only the unique compounds from each library were included to create the Baselt semi-target library. Similarly, the Baselt semi-target library was then combined with the HighResNPS library to create the HighResNPS semi-target library. These libraries were then converted to a Waters Corporation UNIFI library format (.ulc) and applied to special cases submitted in 2021–2022.

The Baselt semi-target library consisted of 2690 compounds of which 925 were unique to the Baselt library while the HighResNPS semi-targeted library consisted of 4242 compounds of which, 1552 were unique to the HighResNPS library. The application of the Baselt semi-target library to selected special cases resulted in the detection of compounds like vortioxetine, darunavir, abacavir, zonisamide, drotaverine and brexpiprazole were detected in blood. Similarly, 3-Me-PCPy and 5F-3,5-AB-PFUPPYCA were detected in seized material using the HighResNPS semi-target library.

The use of only the in-house targeted libraries would have missed these relevant compounds in both forensic toxicology and forensic chemistry contexts. The use of InChIKeys rather than compound names or other standard identifiers made it easy to identify the unique compounds in each of the selected libraries with little effort and thus increased the scope by 52% and 140% relative to the target library.

Inclusion of InChIKeys in target libraries offers the possibility for laboratories to synchronize their libraries with libraries from other laboratories to broaden their screening capacity.