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

Abstract

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.

Development and Evaluation of a Synthetic Opioid Targeted Gas Chromatography Mass Spectrometry (GC-MS) Method

“…A previously published framework for the development and evaluation of the targeted synthetic opioid method was used for this work [32]. Briefly, method development began with investigation of the six different column stationary phases to establish which phase provided the best balance of retention time differentiation, sensitivity, and total analysis time (Step 1).…”

“…Unless otherwise noted, the standard spectral tune (stune) was used along with an MS scan range of m/z 50 to m/z 450, a scan speed of N = 2, and a threshold of 150 counts. Data analysis protocols from [32] were employed. MassHunter (Agilent Technologies) was used for chromatographic peak integration and AMDIS (NIST, Gaithersburg, MD, USA) for chromatogram deconvolution and mass spectral quality analysis.…”

“…In this work, we look at complimenting these data-focused approaches by establishing a GC-MS instrumental method specifically for the confirmation of synthetic opioids. The method was developed and evaluated using a previously deployed framework [32] with the goals of (1) minimizing overlapping retention time acceptance windows, (2) understanding how to alter sensitivity of the method without effecting reproducibility, and (3) measuring and documenting the limitations of the method in regards to compound discrimination. Using a test solution consisting of eleven compounds, the method was developed by investigating column type, flow rate, temperature program, inlet, and mass spectrometer source conditions.…”

Comparing two seized drug workflows for the analysis of synthetic cannabinoids, cathinones, and opioids

“…The targeted methods were created using a previously published framework [5] and were developed for each of the three compound classes investigated. Discussion on the development of the targeted methods is provided elsewhere [5,13], and the actual instrument methods are provided in Supplemental Table 4. All analyses were completed using an Agilent 7890/5977B GC-MS with helium as the carrier gas.…”

The min-max test: an objective method for discriminating mass spectra

“…20 The min-max test was initially formulated during our recent work developing targeted gas chromatography-mass spectrometry methods for identifying synthetic cannabinoids 21 and cathinones. 22 We needed to determine if we could discriminate several pairs of closely eluting compounds based on their mass spectra. We wanted to avoid the ambiguity of threshold setting with a similarity score test and the subjectivity of visual comparison with manual interpretation.…”