The Utility of Multi-Dimensional Liquid Chromatography for the Analysis of Seized Drugs: Application to Emerging Drugs

As submitted by the proposer: The purpose of this project is to investigate the use of multi-dimensional liquid chromatography for forensic drug analysis, using emerging drugs as model compounds. The goal of this research would be to ascertain whether multi-dimensional liquid chromatography can greatly enhance the ability to identify emerging drugs. Emerging drugs are synthetically produced alterations of the controlled drugs in order to circumvent laws banning their use as recreational drugs. These modifications often result in structural analogues, structural homologues, positional isomers and stereoisomers. The identification of existing and new emerging drugs is complicated by the similarity in structure, lack of reference materials, insufficient libraries, lack of molecular ions for certain solutes (EI MS), similarity in MS spectra for diastereomers and positional isomers (EI MS, ESI MS-MS) and incomplete chromatographic separations. For these circumstances chromatographic resolution becomes particularly important. Although GC has inherently higher resolving power (peak capacity) than liquid chromatographic techniques (e.g. HPLC, UHPLC, UHPSFC), the former technique is disadvantageous for solutes that are thermally labile, polar and non-volatile. One means of achieving peak capacities equal or greater than GC is to employ a multi-dimensional liquid chromatography technique, such as two dimensional liquid chromatography. The main advantage of two dimensional chromatography versus one dimensional chromatography is the product rule, whereby under ideal conditions the peak capacity of a two dimensional separation is equal to the product of the first resolving dimension (1D) and the second resolving dimension (2D) peak capacities. Although UHPLC has inherently lower one dimension peak capacity, it’s significantly greater selectivity due to mobile phase effects can result in liquid phase separations comparable to GC. Therefore two dimensional UHPLC has the ability to obtain superior separations to one dimensional GC, without the disadvantages of the latter technique. This would be particularly advantageous for the analysis of emerging drugs. Emerging drugs such as synthetic cannabinoids, bath salts, and phenethylamines will be investigated. For the project a trap and elute multi-dimensional approach (two separation columns and a trapping column) with at-column dilution will be investigated. Overall resolution between one dimensional and multidimensional separations employing trap and elute technology with on-column dilution, will be compared for the various drug classes. Developed multi-dimensional liquid chromatographic systems will be tested with simulated samples. The acceptance of UPSFC as viable technique would significantly enhance forensic drug analysis. Note: This project contains a research and/or development component, as defined in applicable law. ca/ncf