title: Structure-related related new approach in the gas chromatography/mass spectrometry analysis of cathinone type synthetic drugs.
abstract: A novel, structure-related derivatization principle has been developed in order to quantify cathinone-type synthetic drugs (CTSDs), focusing on the most common pentedrone (PENT), including also 4-fluoromethcathinone (4-FMC), methcathinone (MCTN), 4-methylethcathinone (4-MEC), 3,4-dimethylmethcathinone (3,4-DMMC), and 4-ethylmethcathinone (4-EMC). Firstly, oximated and, secondly, trimethylsilylated CTSD derivatives were characterized by mass fragmentation patterns using GC/MS that led to the development of a harmonized, quantitative, two-steps derivatization methodology. The two-step process involved i) oximation with hydroxylamine hydrochloride; and ii) trimethylsilylation with N-methyl-N-(trimethylsilyl)-trifluoroacetamide (MSTFA). Next, the oximated-trimethylsilylated species were characterized by retention and mass fragmentation properties. Due to α-cleavage decomposition at their C1C2bonds without exception, CTSDs uniformely exhibited a structure-related fragmentation pattern. The practical utility of this newly recognized mechanism was validated in urine samples employing an extraction-free and time-, work-, cost- and solvent-effective protocol in accordance with Green Chemistry. The centrifuged urines (10-40μL) were evaporated to dryness, followed by derivatization. The analytical performance of the methodology was characterized by repeatability (RSD%, varying between 1.43% and 5.44%), limit of quantitation (LOQ, 15-24μg/mL), linearity (R2, 0.9976-0.9998) and recovery (97-99%) values. The new principle was tested on drug users' urine: one specimen provided 56.8μg/mL PENT (3.8 RSD%). Simple trimethylsilylation of CTSDs confirmed their special fragmentation patterns, not yet described. The instantenous combination of the primarily formed, characteristic fragments with the mass m/z 44, led to the special equilibrium of products: confirming that direct trimethylsilylation of CTSDs is not suitable for their quantitation.
authors.affiliation: Institutes of Chemistry, Departments of Analytical Chemistry, L. Eötvös University, 1117, Pázmány Péter sétány 1/A, Budapest, Hungary; Doctoral School of Pharmaceutical Sciences, Semmelweis University, 1085, Üllői út 26, Budapest, Hungary.
authors.forename: Borbála
authors.initials: B
authors.lastname: Molnár
authors.affiliation: Institutes of Chemistry, Departments of Analytical Chemistry, L. Eötvös University, 1117, Pázmány Péter sétány 1/A, Budapest, Hungary.
authors.forename: Blanka
authors.initials: B
authors.lastname: Fodor
authors.affiliation: Institutes of Chemistry,Departments of Inorganic Chemistry, L. Eötvös University, 1117, Pázmány Péter sétány 1/A, Budapest, Hungary.
authors.forename: Antal
authors.initials: A
authors.lastname: Csámpai
authors.affiliation: National Institute of Forensic Toxicology, 1146, Varannó utca 2-4, Budapest, Hungary.
authors.forename: Előd
authors.initials: E
authors.lastname: Hidvégi
authors.affiliation: Institutes of Chemistry, Departments of Analytical Chemistry, L. Eötvös University, 1117, Pázmány Péter sétány 1/A, Budapest, Hungary. Electronic address: i.molnar.perl@gmail.com.
authors.forename: Ibolya
authors.initials: I
authors.lastname: Molnár-Perl
mesh_terms: D000470:Alkaloids / Q000032:analysis* / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D014297:Trimethylsilyl Compounds / Q000737:chemistry
chemical_list: D000470:Alkaloids; D004364:Pharmaceutical Preparations; D014297:Trimethylsilyl Compounds; C023665:cathinone
keywords: Cathinone type synthetic drugs; Direct sample preparation; GC/MS; Keto groups' oximation; Trimethylsilylation