Mass spectrometric based investigation of differentially protected Azatryptophan derivatives by using Orbitrap MS: Differentiation of positional isomers under protonation and alkali‐cationization conditions

Among the phencyclidine (PCP) and synthetic cathinone analogs present on the street market, 3-methoxyphencyclidine (3-MeO-PCP) is one of the most popular dissociative hallucinogen drugs, while 3-methylmethcathinone (3-MMC) is a commonly encountered psychostimulant. Numerous 3-MeO-PCP- and 3-MMC-related intoxication cases have been reported worldwide. Identification of the positional isomers of MeO-PCP and MMC families are particularly challenging for clinical and forensic laboratories; this is mostly due to their difficult chromatographic separation (particularly when using liquid chromatography–LC) and similar mass spectrometric behaviors. 3-MeO-PCP and 3-MMC were identified in two powders, detained by two subjects and seized by the police, by different analytical techniques, including liquid chromatography-high-resolution accurate-mass Orbitrap mass spectrometry (LC-HRAM-Orbitrap-MS), and solid deposition gas chromatography-Fourier transform infrared spectroscopy (sd-GC-FTIR). LC-HRAM-Orbitrap-MS allowed us to assign the elemental formulae C18H27NO (MeO-PCP) and C11H15NO (MMC) through accurate mass measurement of the two MH+ ions, and the comparison of experimental and calculated MH+ isotopic patterns. However, MH+ collision-induced product ions spectra were not conclusive in discriminating between the positional isomers [(3-MeO-PCP vs. 4-MeO-PCP) and (3-MMC vs. 4-MMC and 2-MMC)]. Likewise, sd-GC-FTIR easily allowed us to differentiate between the MeO-PCP and MMC positional isomers unambiguously, confirming the presence of 3-MeO-PCP and 3-MMC, due to the high-quality match factor of the experimental FTIR spectra against the target FTIR spectra of MeO-PCP and MMC isomers in a dedicated library. 3-MeO-PCP (in contrast to 3-MMC) was also detected in blood and urine samples of both subjects and analyzed in the context of routine forensic casework by LC-HRAM-Orbitrap-MS following a simple deproteinization step. In addition, this untargeted approach allowed us to detect dozens of phase I and phase II 3-MeO-PCP metabolites in all biological specimens. Analysis of the extracted samples by sd-GC-FTIR revealed the presence of 3-MeO-PCP, thus confirming the intake of such specific methoxy-PCP isomer in both cases. These results highlight the effectiveness of LC-HRAM-Orbitrap-MS and sd-GC-FTIR data in attaining full structural characterization of the psychoactive drugs, even in absence of reference standards, in both non-biological and biological specimens.

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Electrospray Ionization Tandem Mass Spectrometric Study of Protonated and Alkali-Cationized α/ε-Hybrid Peptides: Differentiation of a Pair of Dipeptide Positional Isomers

European Journal of Mass Spectrometry ◽

10.1255/ejms.1431 ◽

2016 ◽

Vol 22 (4) ◽

pp. 181-191

Author(s):

A. Ramesh Babu ◽

G. Raju ◽

C. Purna Chander ◽

B. Shoban Babu ◽

R. Srinivas ◽

...

Keyword(s):

Electrospray Ionization ◽

Mass Spectrometric Study ◽

Mass Spectrometric ◽

Tandem Mass ◽

Positional Isomers ◽

Spectrometric Study ◽

Hybrid Peptides ◽

Tandem Mass Spectrometric

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Mass spectrometry-based identification of ortho-, meta- and para-isomers using infrared ion spectroscopy

The Analyst ◽

10.1039/d0an01119c ◽

2020 ◽

Vol 145 (18) ◽

pp. 6162-6170

Author(s):

Rianne E. van Outersterp ◽

Jonathan Martens ◽

Giel Berden ◽

Valerie Koppen ◽

Filip Cuyckens ◽

...

Keyword(s):

Mass Spectrometry ◽

Drug Metabolism ◽

Mass Spectrometric ◽

Positional Isomers ◽

Ion Spectroscopy ◽

Significant Challenge

Distinguishing positional isomers presents a significant challenge for mass spectrometric analyses, for instance in drug metabolism research. We show that IR ion spectroscopy readily identifies ortho-, meta- and para-isomers.

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The use of LC-Orbitrap MS for the detection of Fusarium masked mycotoxins: the case of type A trichothecenes

World Mycotoxin Journal ◽

10.3920/wmj2012.1405 ◽

2012 ◽

Vol 5 (3) ◽

pp. 271-280 ◽

Cited By ~ 11

Author(s):

H. Nakagawa ◽

S. Sakamoto ◽

Y. Sago ◽

M. Kushiro ◽

H. Nagashima

Keyword(s):

Type A ◽

Mass Spectrometric ◽

Molar Ratio ◽

Spectrometric Analysis ◽

Mass Measurements ◽

Masked Mycotoxins ◽

Accurate Mass Measurements ◽

Type A Trichothecenes ◽

Fragmentation Patterns ◽

Orbitrap Ms

‘Masked mycotoxins’ (mycotoxin glucosides) derived from type A trichothecenes (T-2 toxin and HT-2 toxin) were detected in commercially available maize powder reference material. These novel glucosides were identified as T-2 toxin-glucoside (T2-Glc) and HT-2 toxin-glucoside (HT2-Glc) on the basis of accurate mass measurements of characteristic ions and fragmentation patterns using high-resolution liquid chromatography Orbitrap mass spectrometric analysis. Although their absolute structures were not clarified, 3-OH glucosylation appeared to be the most probable when considering the structure of T-2 toxin and the fragment profiles of each masked mycotoxin. Concomitant detection of deoxynivalenol-3-glucoside (DON-3G) in the same material further supports this probability. According to an extrapolation based on the molar ratio DON-3G/DON (0.059), amounts of T2-Glc and HT2-Glc were estimated to be approximately 24 μg/kg and 41 μg/kg, respectively.

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