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.

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.

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.

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-1 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.

GC-MS differentiation of the six regioisomeric dimethoxybenzoyl-1-pentylindoles: Isomeric cannabinoid substances.

The six regioisomeric 1-pentyl-3-dimethoxybenzoylindoles can be differentiated by a combination of EI-MS and FT-IR spectra. The six regioisomeric 1-n-pentyl-3-(dimethoxybenzoyl)-indoles represent potential designer modifications in the synthetic cannabinoid drug category. The analytical properties and methods of regioisomeric differentiation were developed in this study. The base peaks in these six spectra allow these compounds to be subdivided into three groups of two compounds each, the m/z 334 ion is the base peak for the 2,4- and 2,6-dimethoxybenzoyl isomers (compounds 2 and 4), the 2,3- and 2,5-dimethoxybenzoylindole isomers (compounds 1 and 3) show the m/z 200 ion of base peak intensity and the 3,4- and 3,5-isomers (compounds 5 and 6) show the molecular ion as the base peak, m/z 351. The four isomers having a methoxy group substituted at the ortho position show a unique fragment ion occurring at [M-17](+). An interesting fragment ion at m/z 200 is significant in the 2,3 and 2,5 isomers and completely absent in the 3,4 and 3,5 isomers. Minor peaks for m/z 200 appear in the mass spectra of the 2,4 and 2,6-isomers. This set of regioisomeric compounds was well resolved by capillary gas chromatography on a dimethylpolysiloxane stationary phase. The elution order appears related to the degree of substituent crowding in the dimethoxybenzoyl group. FTIR spectra provide useful data for differentiation among these regioisomeric compounds. Infrared absorption spectral data provide distinguishing and characteristic information to individualize the regioisomers in this set of compounds.

Selective determination of dimenhydrinate in presence of six of its related substances and potential impurities using a direct GC/MS method.

A novel simple, direct and selective gas chromatography-mass spectrometry (GC/MS) procedure was developed for the determination of the antihistamine drug dimenhydrinate (DMH) in presence of six of its related substances and potential impurities, namely, diphenylmethane, diphenylmethanol, benzophenone, orphenadrine, caffeine and 8-chlorocaffeine. The method involved resolution of the underivatized compounds using a trifluoropropylmethyl polysiloxane (Rtx-200) capillary column and the mass spectrometric detection was carried out in the electron-impact (EI) mode. Excellent baseline separation of DMH and the cited related substances was achieved in less than 15 min. Quantification of the parent drug DMH was based on measuring its peak area. The reliability and analytical performance of the proposed method were validated with respect to linearity, range, precision, accuracy, specificity, robustness, detection and quantification limits. Calibration curve of DMH was linear over the range 50-500 µg/mL with determination coefficient (R (2)) = 0.9982. The proposed method was successfully applied for the assay of DMH in tablets dosage form with recoveries >96.80%.

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

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.

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.

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.

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

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.

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

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.

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

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.

Mass Spectral and Chromatographic Studies on Some Halogenatedphenyl-2-Piperazinopropanones.

Gas chromatography-mass spectrometry (GC-MS) studies on the halogenatedphenyl-2-piperazinopropanones (XPPPOs): Twelve XPPPOs were subdivided into four groups of compounds and studied using GC-MS. The four studied groups include the three ring-substituted fluorophenylpiperazinopropanones, chlorophenylpiperazinopropanones, bromophenylpiperazinopropanones and trifluoromethylphenylpiperazinopropanones. The three compounds in each group have equal mass and many common mass spectral fragment ions. Perfluoroacylation of the secondary amine nitrogen of these isomeric piperazines gave mass spectra with differences in relative abundance of some fragment ions but acylation did not alter the fragmentation pathway and did not provide additional MS fragments of discrimination among these isomers. The perfluoroacyl derivatives of these piperazines were resolved on a stationary phase of 100% trifluoropropyl methyl polysiloxane (Rtx-200).

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

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.

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

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.

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

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.

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

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.

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

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).

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

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.

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

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.

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

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.

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

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.