Younis Abiedalla

Synthesis and GC–MS analysis of a series of homologs and regioisomers of 3,4-methylenedioxypyrovalerone (MDPV)

A series of ten homologous and regioisomeric aminoketones related to the designer synthetic cathinone derivative MDPV were evaluated in this study. These compounds were prepared from a common precursor chemical, piperonal (3,4-methylenedioxybenzaldehyde). These aminoketones show major peaks in their mass spectra corresponding to the regioisomeric and homologous immonium cation fragments from the loss of the methylenedioxybenzoyl radical species. All ten compounds in this study show equivalent EI MS fragments for the 3,4-methylenedioxybenzoyl fragments (m/z 149) and the methylenedioxybenzene fragment at m/z 121. The m/z 149 results from ionization of the carbonyl oxygen followed by an alpha-cleavage fragmentation. The loss of CO from this ion yields the m/z 121 fragments common to all spectra. The regioisomeric aminoketones yield equivalent mass spectra including mass equivalent regioisomeric immonium cation base peaks. A subset of these compounds has the same molecular weight and almost identical mass spectra to that of the designer drug MDPV. An evaluation of the effects of homologation on gas chromatographic retention showed that addition of a methylene (CH(2)) in the nitrogen-containing ring increases retention more than the equivalent group added to the alkyl side-chain.

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

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

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

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 (C24H23NO) 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.

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

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.

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

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 (C24H23NO) 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-1. 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-1. The aliphatic stretching bands in the 2900cm-1 region yield a consistent triplet pattern because the N-alkyl substituent tail group remains unchanged for all twelve regioisomers. The asymmetric CH2 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.

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

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.

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

ABSTRACT 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 m/z = 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-HT2B receptors and in contrast to 3-TFMPP, most of these TFMPP–MDBP isomers did not show significant binding at 5-HT1 receptor subtypes. Only the 3-TFMPP-3,4-MDBP (Compound 5) isomer displayed affinity comparable to 3-TFMPP at 5-HT1A receptors (Ki = 188 nmol/L).

EXPRESS: 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

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.

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

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-1 and 1000cm-1 provides a significant number of unique absorption bands characteristic of each individual DMPV regioisomer.