Publications by authors named "Jack DeRuiter"

65 Publications

Structure fragmentation studies of ring-substituted N-trifluoroacetyl-N-benzylphenethylamines related to the NBOMe drugs.

Rapid Commun Mass Spectrom 2020 Feb;34(4):e8593

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA.

Rationale: The halogenated derivatives of N-(2-methoxy)benzyl-2,5-dimethoxyphenethylamine (25-NBOMe) such as the 4-bromo analogue (25B-NBOMe) represent a new class of hallucinogenic or psychedelic drugs. The purpose of this study was to determine the role of the electron-donating groups (halogen and dimethoxy) in the pathway of decomposition for the distonic molecular radical cation in the electron ionization mass spectrometry (EI-MS) process of the trifluoroacetamide (TFA) derivatives.

Methods: The systematic removal of substituents from the 4-halogenated 2,5-dimethoxyphenethylamine portion of the N-dimethoxybenzyl NBOMe analogues allowed an evaluation of structural effects on the formation of major fragment ions in the EI-MS of the TFA derivatives. All six regioisomeric dimethoxybenzyl-substituted analogues (2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-dimethoxy) for the four series of phenethyl aromatic ring substitution patterns were prepared, derivatized and analyzed via gas chromatography coupled with EI-MS.

Results: The analogues yield two unique radical cation fragments from the decomposition of the common distonic molecular radical cation. The substituted phenylethene radical cation (m/z 164) is the base peak or second most abundant ion in all six TFA-2,5-dimethoxyphenethylamine isomers. The dimethoxybenzyltrifloroacetamide radical cation (m/z 263) is the base peak or second most abundant ion in the 2- and 3-monomethoxyphenethylamine isomers. However, the 2- and 3-methoxyphenylethene radical cation (m/z 134) is among the five most abundant ions for each of these twelve isomers. Only one isomer in the phenethylamine series yields the corresponding unsubstituted phenylethene radical cation at m/z 104.

Conclusions: The decomposition of the hydrogen-rearranged distonic molecular radical cation favors formation of the dimethoxybenzyltrifloroacetamide (m/z 263) species for the less electron-rich phenethyl aromatic rings. The addition of electron-donating groups to the aromatic ring of the phenethyl group as in the NBOMe-type molecules shifts the decomposition of the common distonic molecular radical cation to favor the formation of the electron-rich substituted phenylethene radical cation.
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http://dx.doi.org/10.1002/rcm.8593DOI Listing
February 2020

Disubstituted piperazine analogues of trifluoromethylphenylpiperazine and methylenedioxybenzylpiperazine: analytical differentiation and serotonin receptor binding studies.

Forensic Sci Res 2018 5;3(2):161-169. Epub 2018 Apr 5.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.

A series of N,N-disubstituted piperazines were synthesized containing the structural elements of both methylenedioxybenzylpiperazine (MDBP) and trifluoromethylphenylpiperazine (TFMPP) in a single molecule. These six potential designer drug molecules having a regioisomeric relationship were compared in gas chromatography-mass spectrometry (GC-MS), gas chromatography-infrared spectroscopy and serotonin receptor affinity studies. These compounds were separated by capillary gas chromatography on an Rxi®-17Sil MS stationary phase film and the elution order appears to be determined by the position of aromatic ring substitution. The majority of electron ionization mass spectral fragment ions occur via processes initiated by one of the two nitrogen atoms of the piperazine ring. The major electron ionization mass spectrometry (EI-MS) fragment ions observed in all six of these regioisomeric substances occur at / = 364, 229, 163 and 135. The relative intensity of the various fragment ions is also equivalent in each of the six EI-MS spectra. The vapour phase infrared spectra provide a number of absorption bands to differentiate among the six individual compounds on this regioisomeric set. Thus, the mass spectra place these compounds into a single group and the vapour phase infrared spectra differentiate among the six regioisomeric possibilities. All of the TFMPP-MDBP regioisomers displayed significant binding to 5-HT receptors and in contrast to 3-TFMPP, most of these TFMPP-MDBP isomers did not show significant binding at 5-HT receptor subtypes. Only the 3-TFMPP-3,4-MDBP (Compound 5) isomer displayed affinity comparable to 3-TFMPP at 5-HT receptors ( = 188 nmol/L).
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http://dx.doi.org/10.1080/20961790.2018.1445497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197089PMC
April 2018

Gas Chromatography-Mass Spectrometry (GC-MS) and Gas Chromatography-Infrared (GC-IR) Analyses of the Chloro-1- n-pentyl-3-(1-naphthoyl)-Indoles: Regioisomeric Cannabinoids.

Appl Spectrosc 2019 Apr 16;73(4):433-443. Epub 2018 Nov 16.

1 Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.

The analytical differentiation of the indole ring regioisomeric chloro-1- n-pentyl-3-(1-naphthoyl)-indoles is described in this report. The regioisomeric chloroindole precursor compounds, N- n-pentyl chloroindole synthetic intermediates, and the target chloro-substituted naphthoylindoles showed the equivalent gas chromatographic elution order based on the position of chlorine substitution on the indole ring. The regioisomeric chloro-1- n-pentyl-3-(1-naphthoyl)-indoles yield electron ionization mass spectra having equivalent major fragments resulting from cleavage of the groups attached to the central indole nucleus. Fragment ions occur at m/z 127 and 155 for the naphthyl and naphthoyl cations common to all indoles having the naphthoyl group substituted at the indole-3 position. Fragments resulting from the loss of the naphthoyl and/or n-pentyl groups from the molecular radical cation yield the cations at m/z 318, 304, 248, and 178. The characteristic (M-17) fragment ion at m/z 358 resulting from the loss of OH radical is significant in the mass spectra of all these compounds with 1-naphthoyl groups substituted at the indole-3 position. The vapor phase infrared spectra provide a number of characteristic absorption bands to identify the individual isomers.
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http://dx.doi.org/10.1177/0003702818809998DOI Listing
April 2019

Dopaminergic neurotoxic effects of 3-TFMPP derivatives.

Life Sci 2018 Sep 29;209:357-369. Epub 2018 Jul 29.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA. Electronic address:

Designer drugs are synthetically formulated to mimic the psychostimulatory effects of an original controlled/illegal drug of abuse. Designer drugs have similar chemical structure or functional analog as compared to existing controlled psychostimulatory drugs. There is a substantial rise in the production and use of designer drugs globally. Piperazine designer drugs were synthesized as an alternative to MDMA and have shown to induce numerous toxic effects leading to huge health, safety, law enforcement & monetary problems, and lethality. Currently, there are very few studies on the dopaminergic neurotoxicity of 1-(3-trifluoromethylphenyl) piperazine (3-TFMPP) and its derivatives (structural congeners). N27 rat dopaminergic neurons are valid cells to investigate the neurotoxic effects and establish the neurotoxic mechanisms of various substances. In the current study, we studied the time and dose-dependent neurotoxicity mechanisms of dopaminergic neurotoxicity of 3-TFMPP (parent compound) and its derivatives (2-TFMPP, 4-TFMPP). TFMPP derivatives-induced significant neurotoxicity (induced dopaminergic neuronal death. TFMPP derivatives-induced oxidative stress, mitochondrial dysfunction, apoptosis and decreased tyrosine hydroxylase expression. If the use of designer drugs are not strictly regulated and restricted around the world, this can lead to numerous central and peripheral disorders leading to a liability to the current and future society.
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http://dx.doi.org/10.1016/j.lfs.2018.07.052DOI Listing
September 2018

Slow-Binding Inhibition of Mycobacterium tuberculosis Shikimate Kinase by Manzamine Alkaloids.

Biochemistry 2018 08 31;57(32):4923-4933. Epub 2018 Jul 31.

Department of Drug Discovery and Development, Harrison School of Pharmacy , Auburn University , 4306 Walker Building , Auburn , Alabama 36849 , United States.

Tuberculosis represents a significant public health crisis. There is an urgent need for novel molecular scaffolds against this pathogen. We screened a small library of marine-derived compounds against shikimate kinase from Mycobacterium tuberculosis ( MtSK), a promising target for antitubercular drug development. Six manzamines previously shown to be active against M. tuberculosis were characterized as MtSK inhibitors: manzamine A (1), 8-hydroxymanzamine A (2), manzamine E (3), manzamine F (4), 6-deoxymanzamine X (5), and 6-cyclohexamidomanzamine A (6). All six showed mixed noncompetitive inhibition of MtSK. The lowest K values were obtained for 6 across all MtSK-substrate complexes. Time-dependent analyses revealed two-step, slow-binding inhibition. The behavior of 1 was typical; initial formation of an enzyme-inhibitor complex (EI) obeyed an apparent K of ∼30 μM with forward ( k) and reverse ( k) rate constants for isomerization to an EI* complex of 0.18 and 0.08 min, respectively. In contrast, 6 showed a lower K for the initial encounter complex (∼1.5 μM), substantially faster isomerization to EI* ( k = 0.91 min), and slower back conversion of EI* to EI ( k = 0.04 min). Thus, the overall inhibition constants, K*, for 1 and 6 were 10 and 0.06 μM, respectively. These findings were consistent with docking predictions of a favorable binding mode and a second, less tightly bound pose for 6 at MtSK. Our results suggest that manzamines, in particular 6, constitute a new scaffold from which drug candidates with novel mechanisms of action could be designed for the treatment of tuberculosis by targeting MtSK.
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http://dx.doi.org/10.1021/acs.biochem.8b00231DOI Listing
August 2018

GC-MS and GC-IR Analyses of the Methoxy-1-n-pentyl-3-(1-naphthoyl)-indoles: Regioisomeric Designer Cannabinoids.

J Chromatogr Sci 2018 Oct;56(9):779-788

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.

The indole ring regioisomeric methoxy-1-n-pentyl-3-(1-naphthoyl)-indoles represent indole ring-substituted analogs of the synthetic cannabinoid JWH-018. The electron ionization mass spectra show equivalent regioisomeric major fragments resulting from cleavage of the groups attached to the central indole nucleus. The characteristic (M-17)+ fragment ion at m/z 354 resulting from the loss of OH group is significant in the mass spectra of all four compounds. Fragmentation of the naphthoyl and/or pentyl groups yields the cations at m/z 314, 300, 244 and 216. The vapor-phase infrared spectra provide a number of characteristic absorption bands to identify the individual isomers. Gas chromatographic separations on a capillary column containing a film of trifluoropropylmethyl polysiloxane (Rtx-200) provided excellent resolution of these compounds, their precursor indoles and intermediate pentylindoles. The elution order appears related to the degree of crowding of indole ring substituents.
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http://dx.doi.org/10.1093/chromsci/bmy059DOI Listing
October 2018

Correlation of vapor phase infrared spectra and regioisomeric structure in synthetic cannabinoids.

Spectrochim Acta A Mol Biomol Spectrosc 2018 May 20;196:375-384. Epub 2018 Feb 20.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. Electronic address:

The twelve 1-n-pentyl-2-, 3-, 4-, 5-, 6- and 7-(1- and 2-naphthoyl)-indoles each have the same substituents attached to the indole ring, identical elemental composition (CHNO) yielding identical nominal and accurate masses. These twelve isomers cover all possible positions of carbonyl bridge substitution for both indole (positons 2-7) and naphthalene rings (positions 1 and 2). Regioisomeric compounds can represent significant challenges for mass based analytical methods however, infrared spectroscopy is a powerful tool for the identification of positional isomers in organic compounds. The vapor phase infrared spectra of these twelve uniquely similar compounds were evaluated in GC-IR experiments. These spectra show the bridge position on the indole ring is a dominating influence over the carbonyl absorption frequency observed for these compounds. Substitution on the pyrrole moiety of the indole ring yields the lowest CO frequency values for position 2 and 3 giving a narrow range from 1656 to 1654cm. Carbonyl absorption frequencies are higher when the naphthoyl group is attached to the benzene portion of the indole ring yielding absorption values from 1674 to 1671cm. The aliphatic stretching bands in the 2900cm region yield a consistent triplet pattern because the N-alkyl substituent tail group remains unchanged for all twelve regioisomers. The asymmetric CH stretch is the most intense of these three bands. Changes in positional bonding for both the indole and naphthalene ring systems results in unique patterns within the 700 wavenumber out-of-plane region and these absorption bands are different for all 12 regioisomers.
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http://dx.doi.org/10.1016/j.saa.2018.02.052DOI Listing
May 2018

Analytical studies on the 2-naphthoyl substituted-1-n-pentylindoles: Regioisomeric synthetic cannabinoids.

J Chromatogr B Analyt Technol Biomed Life Sci 2018 Mar 31;1077-1078:77-84. Epub 2018 Jan 31.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. Electronic address:

The six 1-n-pentyl-2-, 3-, 4-, 5-, 6- and 7-(2-naphthoyl)-indoles each have the same substituents attached to the indole ring, identical elemental composition (CHNO) yielding identical nominal and accurate masses. The electron ionization mass spectra of the 2-naphthoyl substituted isomers share equivalent major fragment ions resulting from cleavage of the groups attached to the central indole nucleus with some differences in relative abundances. These six regioisomers were successfully resolved on an Rtx-5 and Rxi-17Sil MS stationary phases and the molecules having both substituent groups on the same side of the indole ring (1,2- and 1,7-substituents) show the least retention. The more linear molecules have higher relative retention properties. A comparison of the GC properties of the 1-naphthoyl- and 2-naphthoyl groups attached at identical positions of the indole ring showed higher GC retention for the 2-naphthoyl substituted isomer in all cases evaluated. The amide inverse isomers (1-naphthoyl-3-n-pentylindoles) were separated from the 1-n-pentyl-3-naphthoyl-indoles on an Rtx-200 stationary phase. The two inverse amide isomers having the 1- and 2-naphthoyl groups substituted at the 1-position of the indole ring elute before either of the N-alkyl-indole isomers having the 1- and 2-naphthoyl groups substituted at the 3-position of the indole ring. The amide inverse isomers yield EI mass spectra easily distinguishing these amides from the ketone isomers having the naphthoyl groups at the indole 3-position.
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http://dx.doi.org/10.1016/j.jchromb.2018.01.036DOI Listing
March 2018

Comparing the dopaminergic neurotoxic effects of benzylpiperazine and benzoylpiperazine.

Toxicol Mech Methods 2018 Mar 28;28(3):177-186. Epub 2017 Sep 28.

a Department of Drug Discovery and Development , Harrison School of Pharmacy, Auburn University , Auburn , AL , USA.

Benzylpiperazine has been designated as Schedule I substance under the Controlled Substances Act by Drug Enforcement Administration. Benzylpiperazine is a piperazine derivative, elevates both dopamine and serotonin extracellular levels producing stimulatory and hallucinogenic effects, respectively, similar to methylenedioxymethamphetamine (MDMA). However, the comparative neurotoxic effects of Piperazine derivatives (benzylpiperazine and benzoylpiperazine) have not been elucidated. Here, piperazine derivatives (benzylpiperazine and benzoylpiperazine) were synthesized in our lab and the mechanisms of cellular-based neurotoxicity were elucidated in a dopaminergic human neuroblastoma cell line (SH-SY5Y). We evaluated the in vitro effects of benzylpiperazine and benzoylpiperazine on the generation of reactive oxygen species, lipid peroxidation, mitochondrial complex-I activity, catalase activity, superoxide dismutase activity, glutathione content, Bax, caspase-3, Bcl-2 and tyrosine hydroxylase expression. Benzylpiperazine and benzoylpiperazine induced oxidative stress, inhibited mitochondrial functions and stimulated apoptosis. This study provides a germinal assessment of the neurotoxic mechanisms induced by piperazine derivatives that lead to neuronal cell death.
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http://dx.doi.org/10.1080/15376516.2017.1376024DOI Listing
March 2018

Differentiation of the six dimethoxypyrovalerone regioisomers: GC-MS, GC-MS/MS and GC-IR.

Talanta 2017 Aug 3;171:220-228. Epub 2017 May 3.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. Electronic address:

Multiple and complementary analytical methods are often necessary for the identification of a specific compound from a series of closely related structural isomers. Gas chromatography-mass spectrometry (GC-MS), gas chromatography-product ion mass spectrometry (GC-MS/MS) and gas chromatography-infrared spectroscopy (GC-IR) were used to differentiate between the six dimethoxypyrrovalerone (DMPV) regioisomers. The six regioisomeric aminoketones were separated on a 50% phenyl stationary phase and the elution order is related to the positioning of substituents on the aromatic ring. These six DMPV regioisomers yield essentially identical mass spectral data in both chemical ionization (CI-MS) and electron ionization (EI-MS) spectra as well as identical product ion MS/MS spectra of the iminium cation base peak (m/z 126). These various mass spectral techniques provide data to identify all major structural features of these molecules except the dimethoxy substitution pattern of the aromatic ring. The region of the vapor phase infrared spectra between 1600cm and 1000cm provides a significant number of unique absorption bands characteristic of each individual DMPV regioisomer.
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http://dx.doi.org/10.1016/j.talanta.2017.04.067DOI Listing
August 2017

GC-MS, GC-MS/MS and GC-IR differentiation of desoxy cathinone derivatives: Cyclic tertiary amines related to MDPV.

J Chromatogr B Analyt Technol Biomed Life Sci 2017 Mar 7;1048:38-48. Epub 2017 Feb 7.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. Electronic address:

The desoxy phenethylamine analogues in this study represent a combination of alkyl side-chain and cyclic amines (azetidine, pyrrolidine, piperidine and azepane) to yield a set of molecules of identical elemental composition as well as major mass spectral fragment ions (base peaks) of identical elemental composition. These desoxy phenethylamine analogues of the aminoketone designer drug, 3,4-methylenedioxy-pyrrovalerone (MDPV) related to the natural product cathinone were prepared from piperonal (3,4-methylenedioxybenzaldehyde) via the intermediate precursor ketones. The aminoketones and the desoxy phenethylamine regioisomers were each separated in capillary gas chromatography experiments using an Rxi-17Sil MS stationary phase with the aminoketones showing greater retention than the corresponding desoxyamines.
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http://dx.doi.org/10.1016/j.jchromb.2017.01.045DOI Listing
March 2017

GC-MS, MS/MS and GC-IR Analysis of a Series of Methylenedioxyphenyl-Aminoketones: Precursors, Ring Regioisomers and Side-Chain Homologs of 3,4-Methylenedioxypyrovalerone.

J Chromatogr Sci 2017 02 12;55(2):99-108. Epub 2016 Oct 12.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA

A combination of GC-MS, MS/MS and GC-IR techniques were used to characterize the ring substitution pattern, the alkyl side-chain and the cyclic tertiary amine portions of a series of six homologous and regioisomeric methylenedioxyphenyl-aminoketones related to the designer drug, 3,4-methylenedioxypyrovalerone (MDPV). Chromatographic retention increases with the hydrocarbon content of the alkyl side-chain and the 3,4-methylenedioxy substitution pattern shows higher retention than the corresponding 2,3-methylenedioxy isomer. The aminoketones show major peaks in their mass spectra corresponding to the homologous series of iminium cation fragments from the loss of the regioisomeric methylenedioxybenzoyl radical species. Deuterium labeling experiments confirm the iminium cation base peaks to undergo the loss of a hydrocarbon molecular fragment to yield product ions characteristic of the side-chain and pyrrolidine ring portion of the parent cathinone derivative. The mass spectra for the designer drug MDPV and its regioisomeric 2,3-methylenedioxy isomer show equivalent fragments including the base peak at m/z 126 and major product ion fragments at m/z 84. The ring substitution pattern for these two isomers was differentiated by characteristic absorption bands in the 1,500 -1,200 cm range in their vapor phase IR. These characteristic bands can also be used to identify the aromatic ring substitution pattern in the regioisomeric precursor ketones.
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http://dx.doi.org/10.1093/chromsci/bmw159DOI Listing
February 2017

Differentiation of cyclic tertiary amine cathinone derivatives by product ion electron ionization mass spectrometry.

Rapid Commun Mass Spectrom 2016 Mar;30(6):763-72

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA.

Rationale: A number of synthetic cathinones (aminoketones, 'bath salts') are tertiary amines containing a cyclic amino group, most commonly pyrrolidine. These totally synthetic compounds can be prepared in a number of regioisomeric designer modifications and many of these can yield isomeric major fragment ions in electron ionization mass spectrometry (EI-MS).

Methods: A series of regioisomeric cyclic tertiary amines were prepared and evaluated in EI-MS and MS/MS product ion experiments. The cyclic amines azetidine, pyrrolidine, piperidine and azepane were incorporated into a series of aminoketones related to the cathinone derivative drug of abuse known as MDPV. Deuterium labeling in both the cyclic amine and alkyl side chain allowed for the confirmation of the structure for the major product ions formed from the EI-MS iminium cation base peaks.

Results: These iminium cation base peaks show characteristic product ion spectra which allow differentiation of the ring and side-chain portions of the structure. The small alkyl side chains favor ring fragmentation in the formation of the major product ions. The higher side-chain homologues appear to promote product ion formation by side-chain fragmentation. Both side-chain and ring fragmentation yield a mixture of product ions in the piperidine and azepane series.

Conclusions: Product ion fragmentation provides useful data for differentiation of cyclic tertiary amine iminium cations from cathinone derivative drugs of abuse. Regioisomeric iminium cations of equal mass yield characteristic product ions for the alkyl side-chain homologues of azetidine, pyrrolidine, piperidine and azepane cyclic amines.
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http://dx.doi.org/10.1002/rcm.7491DOI Listing
March 2016

Product ion tandem mass spectrometric differentiation of regioisomeric side-chain groups in cathinone derivatives.

Rapid Commun Mass Spectrom 2016 07;30(14):1713-1721

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA.

Rationale: Precursor materials are available to prepare aminoketone drugs containing regioisomeric propyl and isopropyl side-chain groups related to the drug alpha-pyrrovalerone (Flakka) and MDPV (3,4-methylenedioxypyrrovalerone). These compounds yield equivalent regioisomeric iminium cation base peaks in electron ionization mass spectrometry (EI-MS).

Methods: The propyl and isopropyl side-chain groups related to alpha-pyrrovalerone and MDPV were prepared and evaluated in EI-MS and tandem mass spectrometry (MS/MS) product ion experiments. Deuterium labeling in both the pyrrolidine and alkyl side-chain groups allowed for the confirmation of the structures for the major product ions formed from the regioisomeric EI-MS iminium cation base peaks.

Results: These iminium cation base peaks show characteristic product ion spectra which allow differentiation of the side-chain propyl and isopropyl groups in the structure. The n-propyl side chain containing iminium cation base peak (m/z 126) in the EI-MS spectrum yields a major product ion at m/z 84 while the regioisomeric m/z 126 base peak for the isopropyl side chain yields a characteristic product ion at m/z 70. Deuterium labeling in both the pyrrolidine ring and the alkyl side chain confirmed the process for the formation of these major product ions.

Conclusions: Product ion fragmentation provides useful data for differentiation of n-propyl and isopropyl side-chain iminium cations from cathinone derivative drugs of abuse. Regioisomeric n-propyl and isopropyl iminium cations of equal mass yield characteristic product ions identifying the alkyl side-chain regioisomers in the pyrrolidine cathinone derivatives. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/rcm.7603DOI Listing
July 2016

GC-MS analysis of the regioisomeric methoxy- and methyl-benzoyl-1-pentylindoles: Isomeric synthetic cannabinoids.

Sci Justice 2015 Sep 18;55(5):291-8. Epub 2015 Mar 18.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. Electronic address:

The regioisomeric 1-n-pentyl-3-(methoxybenzoyl)indoles and the 1-n-pentyl-3-(methylbenzoyl)indoles represent potential designer modifications in the synthetic cannabinoid drug category. These six compounds were prepared by a two-step synthetic method. The analytical properties and methods of regioisomeric differentiation were developed in this study. The molecular ion represents the base peak in the EI mass spectra for most of the compounds in this group. The meta- and para-isomers in each series display fragment ions at equivalent masses with some differences in relative abundance of these ions. The ortho-substituted isomers for both the methoxybenzoyl and methylbenzoyl series show a unique fragment ion occurring at M-17. Deuterium labeling for the methoxy group in the ortho-methoxybenzoyl isomer (ortho-OCD3) confirmed the ortho-substituent as the source of the hydrogen in OH (M-17) elimination. The two sets of regioisomers were well resolved by capillary gas chromatography and the elution order reflected increasing molecular linearity. In both sets of compounds the ortho-isomer eluted first and the para-isomer showed the highest retention time. The HPLC separation showed the ortho-isomer eluting first and the meta-isomer eluting last in both sets of regioisomers.
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http://dx.doi.org/10.1016/j.scijus.2015.02.007DOI Listing
September 2015

Mass spectral studies on 1-n-pentyl-3-(1-naphthoyl)indole (JWH-018), three deuterium-labeled analogues and the inverse isomer 1-naphthoyl-3-n-pentylindole.

Rapid Commun Mass Spectrom 2015 May;29(9):871-7

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA.

Rationale: A number of synthetic cannabinoids such as the 1-alkyl-3-acylindoles are the target of significant designer drug activity. One of the first waves of these compounds identified in clandestine samples was 1-n-pentyl-3-(1-naphthoyl)indole, JWH-018. These totally synthetic molecules can be prepared in a number of regioisomeric forms.

Methods: The electron ionization mass spectrometric (EI-MS) fragmentation of the 1-n-pentyl-3-(1-naphthoyl)indole is compared to its inverse isomer 1-naphthoyl-3-n-pentylindole. These two substances are directly available from indole using identical precursor reagents and similar reaction conditions. Stable isotope deuterium labeling of the three major regions of the JWH-018 molecule allows confirmation of the structures of the major fragment ions. The spectra for the 1-n-pentyl-3-(1-naphthoyl)-d(5) -indole, 1-n-pentyl-3-(1-d(7) -naphthoyl)indole and 1-d(11) -n-pentyl-3-(1-naphthoyl)indole provide significant assistance in elucidating the structures for the major fragment ions in JWH-018.

Results: The EI mass spectra for these isomers show a number of unique ions which allow for the differentiation of the 1-alkyl-3-acylindole compounds from the inverse regioisomeric 1-acyl-3-alkylindoles. The fragment ion [M-17](+) at m/z 324 for JWH-018 was formed by the elimination of a hydroxyl radical and the spectra of the three deuterium-labeled derivatives indicated the loss of hydrogen from the naphthalene ring. Further structural analogues suggest the hydrogen to come from the 8-position of the naphthalene ring.

Conclusions: The three deuterium-labeled analogues provide significant assistance in confirming the structures for the major fragment ions in the mass spectrum of the traditional synthetic cannabinoid compound, 1-n-pentyl-3-(1-naphthoyl)indole, JWH-018. The 1-naphthoyl-3-n-pentylindole inverse regioisomer can be easily differentiated from the traditional synthetic cannabinoid compound.
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http://dx.doi.org/10.1002/rcm.7171DOI Listing
May 2015

GC-MS studies on the six naphthoyl-substituted 1-n-pentyl-indoles: JWH-018 and five regioisomeric equivalents.

Forensic Sci Int 2015 Jul 27;252:107-13. Epub 2015 Apr 27.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. Electronic address:

The GC-MS properties of the synthetic cannabinoid drug of abuse 3-(1-naphthoyl)-1-pentylindole (JWH-018) and all 5 of its' regioisomeric 1-naphthoyl substituted 1-n-pentylindoles are compared in this report. These compounds have the 1-naphthoyl-group attached at each of the possible substituent positions of the indole ring. The six compounds have the same elemental composition C24H23NO and the same substituents attached to the indole ring. The electron ionization mass spectra showed equivalent regioisomeric major fragment ions resulting from cleavage of the groups attached to the central indole nucleus. The characteristic (M-17)(+) fragment ion at m/z 324 resulting from the loss of an OH group was significant in the EI-MS of 3-, 4-, 5- and 6-(1-naphthoyl)-1-pentylindole. Fragment ions occurred at m/z 127 and 155 for the naphthyl and naphthoyl cations common to all six regioisomeric substances. Indole containing fragments produced the cations at m/z 284, 270, 214 and 186. The unique fragment at m/z 141 observed in the 1,2- and 1,7-isomers resulted from a rearrangement involving the two indole substituents to yield the C10H7CH2(+) cation. The major points of EI-MS differentiation of the synthetic cannabinoid JWH-018 from the other five isomers are the high relative abundance of both the m/z 144 ion and the m/z 324 ion in the JWH-018 spectrum. GC separations on a capillary column containing a trifluoropropyl methyl polysiloxane (Rtx-200) stationary phase provided excellent resolution of these six compounds. The elution order appears related to the relative distance between the two indole substituents with the lowest retention associated with minimum distance between the groups attached to the indole nucleus.
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http://dx.doi.org/10.1016/j.forsciint.2015.04.023DOI Listing
July 2015

GC-MS and IR studies on the six ring regioisomeric dimethoxyphenylpiperazines (DOMePPs).

J Forensic Sci 2015 Mar 27;60(2):285-94. Epub 2014 Nov 27.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849; Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.

A number of N-substituted piperazines have been described as drugs of abuse in recent years. This new drug category includes several series of aromatic ring substituted phenylpiperazines. The wide variety of available precursors makes regioisomerism a significant issue in these totally synthetic compounds. In this study, a complete series of regioisomeric dimethoxyphenylpiperazines were synthesized and evaluated using GC-MS and FT-IR. The EI mass spectra show fragments characteristic of both the dimethoxyphenyl and the piperazine portions of the molecules including the dimethoxyphenylaziridinium cation (m/z 180) and dimethoxyphenyl cation (m/z 137). The ion at m/z 56 for the C3H6N(+) fragment is characteristic of the piperazine ring and was observed in all the spectra. The perfluoroacyl derivatives were resolved by GC, and their mass spectra showed some differences in relative abundance of ions. FTIR provides direct confirmatory data for differentiation between the regioisomeric dimethoxyphenylpiperazines, and GC separation was accomplished on an Rtx-200 phase.
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http://dx.doi.org/10.1111/1556-4029.12668DOI Listing
March 2015

GC-MS and FTIR evaluation of the six benzoyl-substituted-1-pentylindoles: isomeric synthetic cannabinoids.

Talanta 2014 Nov 27;129:171-82. Epub 2014 May 27.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, United States. Electronic address:

This report compares the GC-MS and FTIR properties of all 6 regioisomeric benzoyl substituted-1-n-pentylindoles. These compounds have the benzoyl-group attached at each of the possible ring substituent positions of the indole ring. The six compounds have the same elemental composition C20H21NO yielding identical nominal and exact masses. Additionally, the substituents attached to the indole ring, benzoyl- and 1-n-pentyl-groups, are identical for all six isomers. The electron ionization mass spectra show equivalent regioisomeric major fragments resulting from cleavage of the groups attached to the central indole nucleus. Fragment ions occur at m/z 77 and 105 for the phenyl and benzoyl cations common to all six regioisomeric substances. Fragmentation of the benzoyl and/or pentyl groups yields the cations at m/z 234, 220, 214, 186 and 144. While the relative abundance of the ions varies among the six regioisomeric substances the 1-n-pentyl-3-benzoylindole and 1-n-pentyl-5-benzoylindole share very similar relative abundances for the major fragment ions. Chromatographic separations on a capillary column containing a 0.5μm film of 100% trifluoropropyl methyl polysiloxane (Rtx-200) provided excellent resolution of these six compounds. The elution order appears related to the relative distance between the two indole substituted groups. The latest eluting compounds (highest retention time) have the two substituents on opposite sides of the indole nucleus. Infrared absorption spectral data show the carbonyl absorption band for each of the benzoylindoles and provide distinguishing and characteristic information to individualize each of the regioisomers in this set of compounds.
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http://dx.doi.org/10.1016/j.talanta.2014.05.023DOI Listing
November 2014

Synthetic cathinones: "a khat and mouse game".

Toxicol Lett 2014 Sep 25;229(2):349-56. Epub 2014 Jun 25.

Department of Drug Discovery and Development, Auburn University, Auburn, AL 36830, USA. Electronic address:

The birth of the twenty first century has provoked a substantial rise in the use of designer drugs, such as synthetic cathinones, because of a decrease in the availability and purity of other drugs of abuse. The khat plant or Catha edulis, contains cathinone, the parent compound. Synthetic cathinones are sold under the name "bath salts" as a ploy to circumvent legislation from banning their use. Constant modification of the chemical structure by covert laboratories allows manufacturers to stay one step ahead of the legal process. Currently, the widespread distribution of "bath salts" has negative consequences for law enforcement officials and public health resources. Comparable mechanisms of action, between the synthetic cathinones and amphetamine, cocaine, and MDMA are attributed to the similarities in their chemical structures. Synthetic cathinone's potent stimulatory effects, coupled with their high abuse potential, and propensity for addiction demands additional pharmacological and toxicological evaluations for these existing and new designer drugs of abuse. If these drugs are designed carefully, they might also have a significant therapeutic value.
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http://dx.doi.org/10.1016/j.toxlet.2014.06.020DOI Listing
September 2014

Regioisomeric bromodimethoxy benzyl piperazines related to the designer substance 4-bromo-2,5-dimethoxybenzylpiperazine: GC-MS and FTIR analysis.

Forensic Sci Int 2014 Jul 24;240:126-36. Epub 2014 Apr 24.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.

A series of seven regioisomeric bromodimethoxy benzyl piperazines including the designer benzylpiperazine (4-bromo-2,5-dimethoxybenzylpiperazine) were synthesized and their analytical profiles evaluated using GC-MS and FT-IR. The mass spectra for the seven regioisomeric bromodimethoxy benzyl piperazines are almost identical with only the two 2,3-dimethoxy isomers showing one unique major fragment ion at m/z 214/216. Thus, mass spectrometry alone does not provide for the confirmation of identity of any one of the seven compounds to the exclusion of the other isomers. Perfluoroacylation of the secondary amine nitrogen for each of the seven regioisomers gave mass spectra showing some differences in the relative abundance of fragment ions without the appearance of any unique fragments for specific confirmation of structure. Attenuated total reflection infrared spectroscopy provides direct confirmatory data for differentiation between the seven regioisomeric aromatic ring substituted bromodimethoxy benzyl piperazines. Mixtures of the seven piperazine PFP derivatives were successfully resolved via capillary gas chromatography using a relatively polar stationary phase composed of 100% trifluoropropyl methyl polysiloxane.
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http://dx.doi.org/10.1016/j.forsciint.2014.04.019DOI Listing
July 2014

Analytical differentiation of 1-alkyl-3-acylindoles and 1-acyl-3-alkylindoles: isomeric synthetic cannabinoids.

Anal Chem 2014 Apr 27;86(8):3801-8. Epub 2014 Mar 27.

Department of Drug Discovery and Development Harrison, School of Pharmacy, Auburn University , Auburn, AL 36849, United States.

The 1-alkyl-3-acylindoles and the inverse regioisomeric 1-acyl-3-alkylindoles can be prepared directly from a common set of precursor materials and using similar synthetic strategies. The EI mass spectra for these isomers show a number of unique ions which allow for the differentiation of the 1-alkyl-3-acylindole compounds from the inverse regioisomeric 1-acyl-3-alkylindoles. The base peak at m/z 214 in the 1-n-pentyl-3-benzoylindole represents the M-77 cation fragment resulting from the loss of the phenyl group, and this ion is not observed in the inverse isomer. The 1-benzoyl-3-n-pentylindole inverse regioisomer shows a base peak at m/z 105 for the benzoyl cation. Thus, these two base peaks are the result of fragmentation initiated at the carbonyl-oxygen for both isomers. The 1-pentyl-3-benzoylindole is characterized by the strong intensity carbonyl band at 1703 cm(-1), while the amide carbonyl appears as a strong band of equal intensity at 1681 cm(-1) in the 1-benzoyl-3-pentyl regioisomer.
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http://dx.doi.org/10.1021/ac500316xDOI Listing
April 2014

GC-MS and IR studies on the six ring regioisomeric dimethoxybenzoyl-N-methylpiperazines (DMBzMPs).

Forensic Sci Int 2014 Apr 31;237:53-61. Epub 2014 Jan 31.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. Electronic address:

The complete series of regioisomeric dimethoxybenzoyl-N-methylpiperazines were synthesized and evaluated in GC-MS and FTIR studies. The EI mass spectra show fragment ions characteristic of both the dimethoxybenzoyl and the N-methylpiperazine portions of the molecules. These characteristic fragments include the dimethoxybenzoyl cation at m/z 165 as well as the m/z 99 N-methylpiperazine cation and the low mass cation species at m/z 56 (C3H6 N(+)) and the m/z 70 ion (C4H8N(+)). Unique radical cations characteristic for the benzoyl-N-methylpiperazines were observed at m/z 83 (C5H9 N(+)) and m/z 207 (C11H13NO3(+)) Deuterium labeling experiments were used to characterize the mechanism of formation of these fragment ions. Attenuated total reflection infrared spectroscopy provides direct confirmatory data for the differentiation between the six regioisomeric aromatic ring substituted dimethoxybenzoyl-N-methylpiperazines. Gas chromatographic separation of this series of compounds was accomplished on an Rtx-200 stationary phase and relative retention appears related to the degree of steric crowding of the aromatic ring substituents. The most crowded patterns of substitution elute first while the more symmetrical 1-, 3-, 5-substitution pattern has the highest retention time.
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http://dx.doi.org/10.1016/j.forsciint.2014.01.010DOI Listing
April 2014

Elucidating the neurotoxic effects of MDMA and its analogs.

Life Sci 2014 Apr 19;101(1-2):37-42. Epub 2014 Feb 19.

Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA. Electronic address:

Aims: There is a rapid increase in the use of methylenedioxymethamphetamine (MDMA) and its structural congeners/analogs globally. MDMA and MDMA-analogs have been synthesized illegally in furtive dwellings and are abused due to its addictive potential. Furthermore, MDMA and MDMA-analogs have shown to have induced several adverse effects. Hence, understanding the mechanisms mediating this neurotoxic insult of MDMA-analogs is of immense importance for the public health in the world.

Main Methods: We synthesized and investigated the neurotoxic effects of MDMA and its analogs [4-methylenedioxyamphetamine (MDA), 2, 6-methylenedioxyamphetamine (MDMA), and N-ethyl-3, 4-methylenedioxyamphetamine (MDEA)]. The stimulatory or the dopaminergic agonist effects of MDMA and MDMA-analogs were elucidated using the established 6-hydroxydopamine lesioned animal model. Additionally, we also investigated the neurotoxic mechanisms of MDMA and MDMA-analogs on mitochondrial complex-I activity and reactive oxygen species generation.

Key Findings: MDMA and MDMA-analogs exhibited stimulatory activity as compared to amphetamines and also induced several behavioral changes in the rodents. MDMA and MDMA-analogs enhanced the reactive oxygen generation and inhibited mitochondrial complex-I activity which can lead to neurodegeneration. Hence the mechanism of neurotoxicity, MDMA and MDMA-analogs can enhance the release of monoamines, alter the monoaminergic neurotransmission, and augment oxidative stress and mitochondrial abnormalities leading to neurotoxicity.

Significance: Thus, our study will help in developing effective pharmacological and therapeutic approaches for the treatment of MDMA and MDMA-analog abuse.
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http://dx.doi.org/10.1016/j.lfs.2014.02.010DOI Listing
April 2014

Differentiation of the 1-(methylenedioxyphenyl)-2-piperazinopropanes and 1-(methoxyphenyl)-2-piperazinopropanones by GC-IRD and GC-MS.

Forensic Sci Int 2014 Feb 16;235:40-51. Epub 2013 Dec 16.

Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. Electronic address:

Two amphetamine-like piperazine-containing compounds, 1-(3,4-methylenedioxyphenyl)-2-piperazinopropane (3,4-MDPPP), its positional isomer 1-(2,3-methylenedioxyphenyl)-2-piperazinopropane (2,3-MDPPP) and three methcathinone-like piperazine-containing regioisomeric ring substituted 1-(methoxyphenyl)-2-piperazinopropanones (OMePPPOs) have identical elemental composition and no marked differences in their mass spectra. Perfluoroacylation of the secondary amine nitrogen of these isomeric piperazines gave mass spectra with differences in the relative abundance of some fragment ions but did not alter the fragmentation pathway to provide unique ions for discrimination among these isomers. Gas chromatography coupled to infrared detection (GC-IRD) provides direct confirmatory data for the identification of the carbonyl containing compounds and the differentiation of the 3,4-MDPPP from its direct (2,3-MDPPP) and indirect (OMePPPOs) regioisomers. The vapor phase infrared spectra provide for specific confirmation of each of the isomeric piperazines. The perfluoroacyl derivative forms of the five piperazines involved in this study were resolved on two stationary phases, the first is composed of 100% dimethyl polysiloxane (Rtx-1) and the second of 5% diphenyl and 95% dimethyl polysiloxane (Rtx-5).
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http://dx.doi.org/10.1016/j.forsciint.2013.11.015DOI Listing
February 2014

Synthesis and antinociceptive properties of N-phenyl-N-(1-(2-(thiophen-2-yl)ethyl)azepane-4-yl)propionamide in the mouse tail-flick and hot-plate tests.

Bioorg Med Chem Lett 2014 Jan 4;24(2):644-8. Epub 2013 Dec 4.

Department of Pharmacal Sciences, Auburn University Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.

The goals of this study, were to synthesize N-phenyl-N-(1-(2-(thiophen-2-yl)ethyl)azepane-4-yl)propionamide (1c) and determine its antinociceptive properties. The effect of clonidine on 1c antinociception and the involvement of opioid, α2-adrenergic, and I2 imidazoline receptors in 1c antinociception were studied. Also examined was the effect of an endothelin ETA receptor antagonist on 1c antinociception. Synthesis of 1c was accomplished in two steps using modifications of previously reported methods. Antinociceptive (tail-flick and hot-plate) latencies were measured in male Swiss Webster mice treated with 1c; antagonists+1c; clonidine+1c; or antagonists+clonidine+1c. Mice were pretreated with naloxone (opioid antagonist), yohimbine (α2-adrenoceptor antagonist), idazoxan (α2-adrenoceptor/I2-imidazoline antagonist), BU224 (I2-imidazoline antagonist) or BQ123 (endothelin ETA receptor antagonist) to study the involvement of these receptors. Compound 1c produced a dose-dependent increase in antinociceptive latencies; ED50 values were 0.15 mg/kg and 0.16 mg/kg, respectively, in the tail flick and hot plate tests. Naloxone, but not yohimbine, idazoxan or BU224, blocked 1c antinociception. Neither clonidine nor BQ123 potentiated 1c antinociception. Results demonstrate that 1c is 15-times more potent than morphine. The antinociceptive effect of 1c is mediated through opioid receptors. The α2-adrenergic, I2-imidazoline and endothelin ETA receptors are not involved in 1c antinociception.
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http://dx.doi.org/10.1016/j.bmcl.2013.11.069DOI Listing
January 2014

Differentiation of trifluoromethylbenzylpiperazines (TFMBZPs) and trifluoromethylbenzoylpiperazines (TFMBOPs) by GC-MS.

Forensic Sci Int 2013 Dec 8;233(1-3):113-20. Epub 2013 Sep 8.

Dept. of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA; Dept. of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.

Two series of regioisomers - the trifluoromethylbenzylpiperazines (TFMBZPs) and the trifluoromethylbenzoylpiperazines (TMFBOPs) were synthesized and analyzed as potential "hybrid" derivatives of the benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (TMFPP) drugs of abuse. The TFMBZPs are readily differentiated from TMFBOPs by their mass spectra including differences in their mass, the base peaks in their mass spectra as well as several other unique fragment ions. However the mass spectra of each regioisomer in each of these two series have fragment ions of identical mass and thus cannot be differentiated by this analytical method alone. Furthermore, chemical derivatization by perfluoroacylation did not offer any additional unique marker fragment ions in the mass spectrum to allow identification of one regioisomer in a series to the exclusion of the other two regioisomers. The perfluoroacylamides of the regioisomers in the TFMBZP series and the regioisomers in the TMFBOP series were readily separated by GC on the stationary phase Rtx-200 and eluted in an order similar to other perfluoroacyl-derivatives of other benzyl- and benzoylpiperazine compounds reported earlier.
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http://dx.doi.org/10.1016/j.forsciint.2013.09.002DOI Listing
December 2013

Gas chromatography/mass spectrometry analysis of the six-ring regioisomeric dimethoxybenzyl-N-methylpiperazines (DMBMPs).

Rapid Commun Mass Spectrom 2013 Nov;27(22):2551-2558

Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA; Dept. of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.

Rationale: Piperazine-based designer drugs represent a novel class of substances found in illicit drug samples in the US and abroad. The clandestine production of these substances often makes use of piperazine as a key commercially available precursor substance. The commercial availability of 1-methylpiperazine suggests additional designer modification based on this additional precursor material.

Methods: This study focuses on the electron ionization mass spectrometric (EI-MS) fragmentation of the dimethoxybenzyl-N-methylpiperazines as potential designer modifications of the general benzylpiperazine drug skeleton and explores the gas chromatography (GC)/MS properties of all six of these regioisomeric substances.

Results: Fragmentation of the bond between the benzylic carbon and the adjacent piperazine nitrogen provides the base peak in all six spectra. The internal fragmentation within the piperazine ring produces a number of unique ions in the mass spectra of these dimethoxybenzyl-N-methylpiperazines. The migration of methyl groups from nitrogen and oxygen were confirmed by deuterium-labeling experiments.

Conclusions: The six regioisomeric dimethoxybenzyl-N-methylpiperazines yield equivalent fragment ions and deuterium labeling confirmed the elemental composition of the characteristic fragments in their mass spectra. Mixtures of the dimethoxybenzyl-N-methylpiperazines were successfully resolved via capillary gas chromatography using a relatively polar stationary phase and temperature-programming conditions. Copyright © 2013 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/rcm.6716DOI Listing
November 2013

GC-MS and GC-IRD studies on the six ring regioisomeric dimethoxybenzoylpiperazines (DMBzPs).

Forensic Sci Int 2013 Sep 11;231(1-3):54-60. Epub 2013 May 11.

Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.

The dimethoxybenzoylpiperazines show mass spectra characteristic for this set of six regioisomeric substances and the position of ring substitution for the dimethoxy groups can be determined by vapor phase infrared methods. The dimethoxybenzoylpiperazines are characterized by several fragment ions unique to the mass spectra for this set of regioisomeric compounds. Ions at m/z 165 and 182 indicate the presence of the dimethoxybenzoyl and dimethoxybenzamide groups while low mass ions at m/z 56, 69 and 85 are characteristic of the piperazine ring in these isomeric compounds. The mass spectra for these regioisomeric dimethoxybenzoylpiperazines are almost identical and this method alone does not provide for the confirmation of identity of any one of the isomers to the exclusion of the other compounds. The perfluoroacyl derivatives of the six regioisomers were resolved by gas chromatography and their mass spectra showed some differences in relative abundance of fragment ions without the appearance of any unique fragments for specific confirmation of structure. Gas chromatography with infrared detection (GC-IRD) provides direct confirmatory data for the differentiation between the regioisomeric underivatized dimethoxybenzoylpiperazines.
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http://dx.doi.org/10.1016/j.forsciint.2013.04.024DOI Listing
September 2013

GC-MS and GC-IRD studies on the six-ring regioisomeric dimethoxybenzylpiperazines (DMBPs).

Drug Test Anal 2013 Jul 18;5(7):560-72. Epub 2012 Oct 18.

Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA.

Gas chromatography with infrared detection (GC-IRD) provides direct confirmatory data for the differentiation between the six regioisomeric aromatic ring substituted dimethoxybenzylpiperazines (DMBPs). These regioisomeric substances are resolved by GC and the vapour-phase infrared spectra clearly differentiate among the six dimethoxybenzyl substitution patterns. The mass spectra for these regioisomeric substances are almost identical. With only the 2,3-dimethoxy isomer showing one unique major fragment ion at m/z 136. Thus mass spectrometry does not provide for the confirmation of identity of any one of these compounds to the exclusion of the other isomers. Perfluoroacylation of the secondary amine nitrogen for each of the six regioisomers gave mass spectra showing some differences in the relative abundance of fragment ions without the appearance of any unique fragments for specific confirmation of structure. Gas chromatography coupled with time-of-flight mass spectrometric detection (GC-TOF) provided an additional means of confirmation of the elemental composition of the major fragment ions in the mass spectra of these compounds.
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http://dx.doi.org/10.1002/dta.1417DOI Listing
July 2013
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