Synthetic Psychoactive Substances Sorted by LC-MS

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  • Published: Jul 1, 2017
  • Author: Ryan De Vooght-Johnson
  • Channels: HPLC
thumbnail image: Synthetic Psychoactive Substances Sorted by LC-MS

Analysis of new psychoactive substances presents a challenge

There is a growing illicit trade in novel psychoactive substances, a common type of ‘designer drug’, with roughly 100 appearing on the European market each year. These are typically sold over the internet and usually have had little or no safety testing. The sheer numbers of these substances means it is difficult for law enforcement agencies, such as police and customs, as well as hospital emergency departments, to know exactly what they are dealing with.

Traditionally, drug identification has relied on immunoassays, but these are normally only applicable to one compound, so are of little use when several new substances may be present. On the other hand, laboratory analyses using complicated work-up procedures followed by multiple LC-MS methods can give good detection, but require highly trained personnel, so are often not easily carried out at a local level. There is a pressing need for a relatively simple method that can detect multiple psychoactive drugs, i.e. a so-called ‘black-box’.

The Swedish researchers used UHPLC combined with high resolution mass spectrometry (HRMS) in order to detect a wide range of psychoactive drugs. HRMS has the potential to differentiate between isobaric species and in some cases also between isomers where the product ions differ. The researchers examined 120 NPSs, along with 12 naturally occurring alkaloids and 16 legal psychoactive pharmaceutical compounds.

Multiple psychoactive compounds analysed by LC-HMRC

Stock solutions for the various analytes in acetonitrile or methanol were purchased or prepared using authenticated samples. About 18,000 urine samples received for clinical drug testing were investigated, with the anonymity of those involved being preserved. Each sample was diluted five-fold, with nine deuterated internal standards being added: amphetamine, methamphetamine, zopiclone, temazepam, fentanyl, ritalinic acid, methylphenidate, pethidine and pregabalin. UHPLC-HMRC was carried out without any further work-up.

A Dionex UltiMate 3000 system with a YMC UltraHT Hydrosphere-C18 column was used for the UPLC. Gradient elution was performed with 10 mmol aqueous ammonium formate at pH 4.8 and an organic phase of 10 mmol methanolic ammonium formate (both phases with 0.005% formic acid added), with the gradient running from 4 to 95% of the organic phase. A Thermo Scientific UHPLC-Q Exactive high resolution mass spectrometer was used with electrospray ionisation in positive mode, with Thermo Scientific TraceFinder software for data manipulation. Extracted-ion chromatograms (EIC or XIC) were employed to locate the species of interest.

Each analyte was evaluated with respect to one of the nine deuterated internal standards. The method gave good linearity and a typical limit of quantification was 50 ng/ml for most of the compounds examined. It was found that the percentage of false negatives was only 0.3%, while that of false positives was 1.4% per sample and 5.6% per positive sample. Interference from background signals was generally acceptable, although occasionally MS/MS mode was employed (product reaction monitoring, PRM) where this was a particular problem.

In all, 15% of the ca. 18,000 urine samples contained one of the compounds examined, in most cases psychoactive legal pharmaceuticals. These compounds, such as pregabaline, have legitimate medical uses, but may also be abused. The most common NPS was α-PVP (α-pyrrolidinovalerophenone, also known as α-pyrrolidinopentiophenone, ‘gravel’ or ‘flakka’), a psychostimulant banned in many countries, including the UK, USA and Sweden.

New UHPLC-MS method suitable for psychoactive compounds

The new method allows for the detection of a wide range of psychoactive compounds in a single run with minimal sample work-up. Further development is needed to reduce the number of false positives, but the technique may eventually give a method that can be used ‘on-site’ by staff with relatively little training. Such LC-MS techniques need to be employed by health services and law enforcement agencies, since immunoassay methods are inadequate to deal with the wide range of substances that are currently abused.

Related Links

Journal of Mass Spectrometry 2017, Early View paper. Stephanson et al. Use of LC–HRMS in full scan-XIC mode for multi-analyte urine drug testing – a step towards a "black-box" solution?

Wikipedia, alpha-Pyrrolidinopentiophenone

Article by Ryan De Vooght-Johnson

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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