Rapid Targeted Method of Detecting Abused Piperazine Designer Drugs

Abstract

Piperazine derivatives belong to the popular psychostimulating compounds from the group of designer drugs. They are an alternative to illegal drugs such as ecstasy and amphetamines. They are being searched by consumers for recreational use due to their stimulating and hallucinogenic effects. Many NPS-related poisonings and deaths have been reported where piperazines have been found. However, a major problem is the potential lack of laboratory confirmation of the involvement of piperazine derivatives in the occurrence of poisoning. Although many methods have been published, piperazine derivatives are not always included in a routine analytical approach or targeted toxicological analysis. There is an increasing need to provide qualitative evidence for the presence of piperazine derivatives and to ensure reproducible quantification. This article describes a new rapid method of detecting piperazine derivatives in biological material, using LC-MS. All target analytes were separated in a 15 min run time and identified based on the precursor ion, at least two product ions, and the retention time. Stable isotopically labeled (SIL) internal standards: BZP-D7, mCPP-D8 and TFMPP-D4 were used for analysis, obtaining the highest level of confidence in the results. The proposed detection method provides the analytical confirmation of poisoning with piperazine designer drugs.

Comparison of LC-MS and LC-DAD Methods of Detecting Abused Piperazine Designer Drugs

“…Detailed method description and results obtained, such as measures of standards and biological samples, and validation parameters, e.g., regression equations, linear ranges, determination coefficient, analytical limits, quality control parameters, are described in the separate report [ 22 ]. The LC-MS method also confirmed the reproducibility of fragmentation for the tested compounds.…”

“…The method of detection abused piperazine designer drugs in biological material using LC-MS was the subject of a separate publication [ 22 ]. The present article lists the results and stages of the described methodology, which are the most important from the point of view of comparing the LC-MS and LC-DAD methods.…”

“…The values of the working parameters of the mass spectrometer were as follows: the heater block temperature was 400 °C, the desolvation line (DL) temperature was 250 °C, the nebulizing gas flow was 3 L/min, the drying gas flow was 10 L/min and heating gas flow was 10 L/min. Dynamic multiple reaction monitoring (MRM) mode was used and two MRM transitions were selected for each compound [ 22 ].…”

“…Piperazine designer drugs show affinity for many 5-HT receptor subtypes [ 9 , 21 , 22 ]. Their hallucinogenic properties are the result of interaction with the 5-HT2A receptor, which may additionally lead to changes in the functioning of sensory processes [ 4 , 23 ].…”

“…Bruxism, trismus, headaches and dizziness, dissociative symptoms, as well as hyponatraemia, hyperkalaemia and metabolic acidosis are also observed [ 10 , 11 , 17 , 24 , 26 , 27 , 29 , 33 , 41 ]. Analytical evidence of the participation of piperazine designer drugs is needed for a comprehensive diagnosis [ 22 ]. This is all the more difficult as the concentrations in biological fluids may not be closely related to the clinical symptoms found [ 11 , 17 , 27 , 33 ].…”