NBOMe Designer Drugs: GC-MS and LC-QTOF/MS Detection on Blotter Paper by Brazilian Federal Police (Rio Grande do Sul, Brazil)

The NBOMes are classified as new psychoactive substances and have recently become popular as drugs of abuse, being associated with several intoxication cases and even deaths, leading to its ban in several countries. Until now, the most widely used analytical instrument among forensic laboratories in Brazil is GC-MS. In this study, this instrumentation was employed for routine analyzes of twenty blotter paper seizure by Brazilian Federal Police (BFP) in the southernmost state of the country. However, to acquire more information about these samples, LC-QTOF/MS was used as a supplementary analysis to determinate degradation products, metabolites and unknown compounds. The GC-MS analysis detected only 25B-NBOMe, while the LC-QTOF/MS analysis detected 25B-NBOMe, 2C-B and MDMA. The compounds found in these analyzes are quite different from that found 194 Brazilian Journal of Forensic Sciences, Medical Law and Bioethics 7(3):193-204 (2018) C. A. Y. Wayhs et al. in the national profile of seizures by BFP, suggesting that another rout or supplier act in this region. For research and drug intelligence purposes the use of more versatile, sensitive and specific analytical tool provides a greater number of information that could be employed as a valuable strategy in the drug trafficking combat.


Introduction
New psychoactive substances (NPS), also known as designer drugs, has become an issue regarding public health in many parts of the world, demanding constant improvements on the chemistry, pharmacology and toxicology of such substances and on their legal regulation as well [1][2][3] . As a consequence of globalization, when a NPS is discovered or synthesized it is rapidly revealed to the entire world by "dark net" 4,5 . In this context, United Nations' world drug annual report 2017 indicate that the NPS market continues to be very dynamic and is characterized by the emergence of Another factor is due to the versatility of the changes occurring in the molecules and the speed with which they appear in the market, being faster the development of new molecules than the tools for unequivocal identification and even faster than them have been placed under international control 6 . Among the wide variety of NPS, the NBOMe designer drugs ( Figure 1) have been attracting attention from medical and legal issues, due to its association with several intoxication cases and even deaths, leading to its ban in several countries, including Brazil 1,6-8 .

Samples
The sample set consisted of twenty blotter papers proceeding from a single BFP seizure performed in 2016.

Sample preparation
For GC-MS analysis the entire samples of each blotter papers were extracted with 3 mL of methanol by sonication for 3 min in ultrasonic bath and after were vortexed for 1 min. 1 mL of the resulting supernatant solution was transferred to a GC vial ready for injection.

GC-MS
Chromatographic separation was performed on an Agilent 6890 N gas chromatograph coupled to an Agilent 5973 mass selective detector (Agilent

Sample preparation
For LC-QTOF/MS, an aliquot of the methanolic solution of entire samples was diluted with a Methanol:Water solution (50:50). After dilution, the tubes were vortexed for 30 seconds, centrifuged at 2600 g for 7 minutes at 25°C. 1.5 mL of the supernatant from each sample was transferred to an amber vial with a capacity of 1.5 mL. An aliquot of 10 µL were diluted with 990 µL of water containing 0.1% of formic acid.

LC-QTOF/MS
LC-QTOF/MS was used to carry out qualitative analysis. The system was composed of a LC Agilent 1260 Infinity (Agilent Technologies, Palo Alto, CA, USA) and mass spectrometer 5600 TripleTOF system (Sciex, Framingham, MA, US).
Chromatographic separation was performed using an analytical column Waters X- Mass spectrometer source dependent parameters were set as follows:

Results and discussion
NBOMes have recently become popular as drugs of abuse 9 Table 2.      This analytical finding suggest that another routs of synthesis and a bigger range of raw material, excipients and active ingredients must be monitored, following the trends of drug dealers, once it is known that MDMA can be synthesized from different synthesis routes. In this context, chemical profile studies have been determined different contaminants or synthetic impurities, such as co-products, for example, may point to the use of one or the other pathway to obtain MDMA 11,12 . The 2C-B seems to be the most important substances within the substituted phenethylamines class of designer drugs and 25B-NBOMe appears as its novel and highly potent derivative 13 . In these samples, the presence of 2C-B may be seen as a synthesis residue, probably being an excess of precursor that has not been consumed during the reaction of 25B-NBOMe production.
2C-B is a synthetic psychedelic drug that is structurally related to mescaline and was first synthesized in the mid-1970s 14  To date, only few and very recently papers about blotter paper samples seizures in Brazil were published 1,9,13,[24][25][26] . The present study is a small start in the sense of to know the actual scenario of the blotter paper drug market. It is necessary to perform studies with large range of samples and, although the quantification it is not mandatory for legal purposes, it is recommended that researches in this field have incentives. From forensic intelligence point of view these information brings a soft but valuable assistance for the investigation, prevention and combating of drugs trafficking.

Conclusions
In