Revealing Unknown Controlled Substances and New Psychoactive Substances Using High-Resolution LC-MS/MS Machine Learning Models and the Hybrid Similarity Search Algorithm.

Abstract

High-resolution LC-MS/MS tandem mass spectra-based machine learning models are constructed to address the analytical challenge of identifying unknown controlled substances and new psychoactive substances (NPS s). Using a training set comprised of 770 LC-MS/MS barcode spectra (with binary entries 0 or 1) obtained generally by high-resolution mass spectrometers, three classification machine learning models were generated and evaluated. The three models are artificial neural network (ANN), support vector machine (SVM), and k-nearest neighbor (k-NN) models. In these models, controlled substances and NPS s were classified into 13 subgroups (benzylpiperazine, opiate, benzodiazepine, amphetamine, cocaine, methcathinone, classical cannabinoid, fentanyl, 2C series, indazole carbonyl compound, indole carbonyl compound, phencyclidine, and others). Using 193 LC-MS/MS barcode spectra as an external test set, accuracy of the ANN, SVM, and k-NN models were evaluated as 72.5%, 90.0%, and 94.3%, respectively. Also, the hybrid similarity search (HSS) algorithm was evaluated to examine whether this algorithm can successfully identify unknown controlled substances and NPS s whose data are unavailable in the database. When only 24 representative LC-MS/MS spectra of controlled substances and NPS s were selectively included in the database, it was found that HSS can successfully identify compounds with high reliability. The machine learning models and HSS algorithms are incorporated into our home-coded AI-SNPS (artificial intelligence screener for narcotic drugs and psychotropic substances) standalone software that is equipped with a graphic user interface. The use of this software allows unknown controlled substances and NPS s to be identified in a convenient manner.