Predicting the retention time of Synthetic Cannabinoids using a combinatorial QSAR approach

Abuse of Synthetic Cannabinoids (SCs) has become a serious threat to public health. Due to the various structural and chemical group modified by criminals, their detection is a major challenge in forensic toxicological identification. Therefore, rapid and efficient identification of SCs is important for forensic toxicology and drug bans. The prediction of an analyte's retention time in liquid chromatography is an important index for the qualitative analysis of compounds and can provide informatics solutions for the interpretation of chromatographic data.

In this study, experimental data from high-resolution mass spectrometry (HRMS) are used to construct a regression model for predicting the retention time of SCs using machine learning methods. The prediction ability of the model is improved by adopting a strategy that combines different descriptors in different independent machine-learning methods.

The best model was obtained with a method that combined Substructure Fingerprint Count and Finger printer features and the support vector regression (SVR) method, as it exhibited an R² value of 0.81 for the validation set and 0.83 for the test set. In addition, 4 new SCs were predicted by the optimized model, with a prediction error within 3%.

Our study provides a model that can predict the retention time of compounds and it can be used as a filter to reduce false-positive candidates when used in combination with LC-HRMS, especially in the absence of reference standards. This can improve the confidence of identification in non-targeted analysis and the reliability of identifying unknown substances.