Development and evaluation of a synthetic opioid targeted gas chromatography mass spectrometry (GC-MS) method.

As seized drug casework becomes increasingly complex due to the continued prevalence of emerging drugs, laboratories are often looking for new analytical approaches including developing methods for the analysis of specific compounds classes. Recent efforts have focused on the development of targeted gas chromatography mass spectrometry (GC-MS) confirmation methods to compliment the information-rich screening results produced by techniques like direct analysis in real time mass spectrometry (DART-MS). In this work, a method for the confirmation of synthetic opioids and related compounds was developed and evaluated. An 11-component test solution was used to develop a method that focused on minimizing overlapping retention time acceptance windows and understanding the influence of instrument parameters on reproducibility and sensitivity. Investigated settings included column type, flow rate, temperature program, inlet temperature, source temperature, and tune type. Using a DB-200 column, a 35-min temperature ramped method was created. It was evaluated against a suite of 222 synthetic opioids and related compounds, and successfully differentiated all but four compound pairs based on nonoverlapping retention time acceptance windows or objectively different mass spectra. Compared to a general confirmatory method used in casework, the targeted method was up to 25 times more sensitive and provided at least a two-fold increase in retention time differences. Analysis of extracts from actual case samples successfully demonstrated utility of the method and showed no instance of carryover, although the high polarity column required wider retention time windows than other columns.

Development and evaluation of a synthetic cathinone targeted gas chromatography mass spectrometry (GC-MS) method.

To address challenges associated with the increased prevalence of novel psychoactive substances (NPSs), laboratories often adopt new techniques or new methods with the goal of obtaining more detailed chemical information with a higher level of confidence. To demonstrate how new methods applied to existing techniques can be a viable approach, a targeted gas chromatography mass spectrometry (GC-MS) method for synthetic cathinones was developed. To create the method, a range of GC-MS parameters were first investigated using a seven-component test solution with the goal of minimizing compounds with overlapping acceptance windows by maximizing retention time differences within a reasonable runtime. Once developed, the targeted method was evaluated through several studies and was compared to a general GC-MS confirmatory method. The method produced a twofold increase in retention time differences of the test solution compounds with a 3.83-min shorter runtime than the general method. Limitations of the method were also studied by analyzing an additional forty-eight cathinones to identify instances where definitive compound identification may not be possible due to overlapping acceptance windows and mass spectra. Thirty-eight pairs of compounds had retention times differences of less than 2% and, of those thirty-eight, one pair had indistinguishable mass spectra. A set of case samples were also analyzed using the method to evaluate suitability for casework. An increase in split ratio was required to obtain acceptable sensitivity. The development of this method is part of a larger project to measure benefits and drawbacks of different drug chemistry workflows.

A framework for the development of targeted gas chromatography mass spectrometry (GC-MS) methods: Synthetic cannabinoids.

With the increased presence of novel psychoactive substances (NPSs) in casework, drug analysis has become more challenging. To address these challenges, new screening technologies with improved specificity are being implemented, allowing for the creation and adoption of targeted confirmatory analyses that produce more conclusive results. This paper outlines a six-step, data-driven, framework to develop and evaluate gas chromatography mass spectrometry (GC-MS) methods for targeted classes of drugs. The process emphasizes maximizing retention time differences (to minimize the potential for retention time acceptance windows to overlap) and understanding the trade-offs between sensitivity and reproducibility using a test solution containing pairs of compounds that are difficult to distinguish. The method is then evaluated by expanding the panel of compounds analyzed, identifying limitations in compound discrimination, comparing to current methods, and analyzing representative casework to establish usability. To demonstrate this framework, a method for synthetic cannabinoids was created. The developed method utilizes a DB-200 column and an isothermal temperature program. It was found that sensitivity could be adjusted, without compromising reproducibility, by altering the split ratio and injection volume. The targeted method successfully differentiated 50 cannabinoids based on either retention time differences or mass spectral dissimilarity - determined using a newly developed spectral comparison test. Compared to a general method used for casework, the targeted method was an order of magnitude more sensitive, a minute shorter, and provided major increases in retention time differences. This framework can be implemented and adapted to develop targeted methods for other applications or compound classes.