Drugs like amphetamine, methamphetamine, or 3,4-methylenedioxy-N-methamphetamine (MDMA) are known as amphetamine-type stimulants (ATS) [ 1 ]. Based on reported seizures, they are the most prevalent drugs after cannabis and cocaine in Europe [ 2 ]. Especially amphetamines and MDMA are predominantly found in northern and eastern Europe [ 2 ]. While most of the amphetamine production takes place in Belgium, the Netherlands, and Poland, methamphetamine is mainly produced in the Czech Republic [ 2 ]. For MDMA, the main production takes place in the Netherlands and Belgium [ 2 ]. The most common synthesis route for the illicit production of amphetamine is the Leuckart method [ 3 ]. The preferred production method of methamphetamine is the Nagai route and the production via Birch reduction [ 3 ]. While the usage of the Leuckart method for MDMA is known, most frequently the reductive amination with methylamine, hydrogen, and platinum dioxide catalyst is utilized [ 3 ]. Amphetamine is usually produced from the precursor phenylacetone (BMK or benzyl methyl ketone) [ 3 ]. In the case of methamphetamine, ephedrine and pseudoephedrine is a common choice [ 3 ]. For MDMA, piperonyl methyl ketone (PMK) is chosen frequently [ 3 ]. In order to circumvent the transport of scheduled precursor chemicals like BMK, producers started to utilize non-scheduled pre-precursors [ 2 ]. This is done, because most pre-precursors are not “scheduled” monitored. As the first step, a pre-precursor is converted to the needed precursor that is afterwards applied to produce the drug itself. In recent years, one of the most relevant pre-precursors turned out to be alpha-phenylacetoacetonitrile (APAAN) [ 4 ]. APAAN is converted into BMK which is then utilized to produce amphetamine. These pre-precursors extend the possible compounds that can be found at clandestine laboratories. Therefore, interpretation of results is aggravated. This in turn, can imply the need for powerful analytical techniques in order to keep pace. In general, the investigation of clandestine laboratories is highly complex, since every laboratory has a unique setup. Examples of these differences can be different equipment to synthesise drugs, purities of chemicals and solvents, carefulness of the producers, and size and complexity of the laboratory itself and many more. Especially for amphetamine, large-scale productions are frequently observed which is supported by seizure data of amphetamine freebase in multiple countries, that originates from the Netherlands [ 4 ]. Due to this large-scale laboratory size, on-site assessment at clandestine laboratories becomes more difficult as the number of samples and their complexity, based on the diverse nature of the target compounds, increase as well. This applies particularly to inactive laboratories that are no longer in use and evidence of a former usage must be proven by taking samples from multiple surfaces. Another reason why trace analysis can be important, is to get quick information about worktops at laboratory storage sites if they are contaminated. This can be a necessary step of self-protection prior to crime scene investigations if highly potent and in non-visible amounts fully active drugs could be present. Some well-known techniques suitable for on-site analysis, are immunoassay drug tests (IDT) [ 5 ], tabletop nuclear magnetic resonance (NMR) spectroscopy [ 6 ], Raman spectroscopy [ 7 ], infrared (IR) spectroscopy [ 8 ], ion mobility spectrometry (IMS) [ 9 ], and mass spectrometry (MS) [ 10 ]. While IR, NMR and Raman spectroscopy are able to analyse known and unknown target compounds, their need for visible amounts of the target compound makes them unsuitable for trace analysis. Therefore, these techniques are not considered for the current evaluation and subsequent IDT, IMS and ambient pressure laser desorption hyphenated mass spectrometry (APLD-MS) are investigated. In addition, these techniques can be seen as representatives for other techniques of a similar complexity in each case. IDTs are fast to use, lightweight and straightforward. They are a well-established method and frequently used in laboratories, driver controls and can even be used by unskilled persons at workplaces [ 5 ]. Furthermore, they enable a fast, easy to use and affordable analysis for specific target compounds. In addition, the result interpretation is straightforward. Possible drawbacks are that mainly sum-parameters results are measured and a linear increase in cost and time if multiple samples should be analysed. IMS with thermal desorption represents portable state-of-the-art tools for surface analysis. It is an approved technique, which is applied for a long time, benefits from fast analysis time and is capable of detecting even traces of a target compound. Most relevant drawbacks are a low resolution, which leads to relative high false alert rates and easy overload which leads to time intensive cleaning [ 11 ]. Current research for on-site equipment is done in the field of direct desorption MS [ 9 ]. Within this field, the coupling of a desorption unit and an MS creates a system that combines benefits from both techniques. While a direct desorption allows for fast sample throughput, the MS enables the investigation of complex samples. For this coupling, multiple techniques are under investigation. In addition, some of these systems also allow to directly investigate suspicious surfaces. This further speeds up sample throughput and allow for spatially resolved surface investigations. The possibility to investigate only small areas of a given surface and bypass sampling swabs, also allows impression/mark preserving analysis to allow further investigations later on. This work focuses on the coupling of MS with laser desorption at ambient pressure, because no auxiliary media, such as gases or liquids, are needed and former research indicates the usefulness of this technique for such applications [removed due to journal double-blind policy] [ 12 14 ]. In addition, APLD-MS as the third technique for on-site detection, is seen as an example of a possible future technique that could be implemented for routine analysis and demonstrated promising results in this field of application. While all three techniques were examined for these target compounds, literature lacks of direct comparisons of on-site samples and practical evaluation over different technology levels. Therefore, the aim of this publication is to compare IDT, IMS, and APLD-MS for trace analysis of amphetamine, methamphetamine and MDMA, intermediates, such as N-formylamphetamine (NFA) that are carried over to the main product [ 3 ], and drug precursors in clandestine laboratories. A benefit of these techniques is their easy on-site usability, compared to other techniques of their technology level. The limits of detection (LODs) were determined, real case scenario samples from former drug synthesis and seized clandestine laboratories are investigated. These samples demonstrate target analytes on complex matrices, resulting from on-site sampling. These real case scenarios aim to support the comparability of the investigated techniques on-site.
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