Current applications of high-resolution mass spectrometry for the analysis of new psychoactive substances: a critical review

Abstract

The proliferation of new psychoactive substances (NPS) in recent years has resulted in the development of numerous analytical methods for the detection and identification of known and unknown NPS derivatives. High-resolution mass spectrometry (HRMS) has been identified as the method of choice for broad screening of NPS in a wide range of analytical contexts due to its ability to measure accurate masses using data-independent acquisition (DIA) techniques. Additionally, it has shown promise for non-targeted screening strategies that have been developed in order to detect and identify novel analogues without the need for certified reference materials (CRMs) or comprehensive mass spectral libraries. This paper reviews the applications of HRMS for the analysis of NPS in forensic drug chemistry, clinical and forensic toxicology. It provides an overview of the sample preparation procedures in addition to data acquisition, instrumental analysis and data processing techniques.Furthermore, it will give an overview of the current state of non-targeted screening strategies with discussion on future directions and perspectives of this technique.3

Clinical value of analytical testing in patients presenting with new psychoactive substances intoxication

“…To protect the instruments and have better results, sample preparation is often necessary prior to sample analysis. The type of sample preparation technique depends on the matrix, on the physical and chemical properties of the investigated analytes and the level of sensitivity and specificity required for a certain analysis . Blood samples can be extracted using methods such as protein precipitation, liquid–liquid extraction, salting‐out assisted liquid–liquid extraction, solid phase extraction or microwave assisted extraction .…”

“…In recent years, untargeted screening using high‐resolution (HR) MS/MS of urine samples has gained attention for the screening of not only classical but also novel substances, such as NPS . Even though the lack of certified reference material and mass spectral libraries still poses a problem, the ability of HR‐MS/MS to determine a compound's or a fragment's mass with sufficiently high accuracy makes it a valuable tool for the identification of NPS . Nonetheless, this technique is specialized, time‐consuming and expensive, and therefore not routinely available in most clinical settings.…”

“…Additionally, the target analytes need to be present at a sufficiently high concentration in order to trigger an acquisition . HR‐MS/MS can be operated in data‐independent acquisition modes, which provide comprehensive full scan MS and MS/MS and qualitatively analyses of samples . These techniques have the additional advantage that data can be retrospectively analysed for new analytes and therefore re‐extraction or re‐analysis of samples is not necessary .…”

“…HR‐MS/MS can be operated in data‐independent acquisition modes, which provide comprehensive full scan MS and MS/MS and qualitatively analyses of samples . These techniques have the additional advantage that data can be retrospectively analysed for new analytes and therefore re‐extraction or re‐analysis of samples is not necessary . Additionally, it is not necessary to have a library with certified reference standards (for the comparison of retention times or mass spectra), thus overcoming the problem of the availability of NPS reference standards.…”

Should NPS be included in workplace drug testing?

“…First, several countries have banned entire classes of NPS, irrespective of their specific chemical structure. [11][12][13] Screening non-targeted analysis for NPS is also taking advantage of the significant advancement of other new technologies, such as assays for the detection of synthetic cannabinoid receptor agonists (SCRAs) based on interactions of the compounds with CB1 and CB2 receptors. [5][6][7] Third, pharmacokinetic studies progressively provide information about the various NPS metabolic pathways and the target analytes to look for, in different biological matrices.…”