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.

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.

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.

Determination of etofibrate, fenofibrate, and atorvastatin in pharmaceutical preparations and plasma using differential pulse polarographic and square wave voltammetric techniques.

Etofibrate, fenofibrate, and atorvastatin were determined in their pharmaceutical preparations and human plasma using differential pulse polarographic and square wave voltammetric techniques by reduction at a dropping-mercury working electrode versus Ag/AgCl reference electrode. The reversibility of the electrode reactions was tested using cyclic voltammetry, and they were found to be irreversible reduction reactions. Optimum conditions such as pH, scan rate, and pulse amplitude were studied, and validation of the proposed methods was performed. The proposed methods proved to be accurate, precise, robust, and specific for determination of the 3 drugs. The relative standard deviation values were <2%, indicating that these methods are precise. Limits of detection and quantitation were in the ranges of 0.037-0.21 and 0.12-0.71 microg/mL, respectively, indicating high sensitivity.

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.

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%.

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.

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 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.

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.

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).

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.

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 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.

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.

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.

Differentiation of methoxybenzoylpiperazines (OMeBzPs) and methylenedioxybenzylpiperazines (MDBPs) By GC-IRD and GC-MS.

The designer drug 3,4-methylenedioxybenzylpiperazine (3,4-MDBP), its positional isomer 2,3-methylenedioxybenzylpiperazine (2,3-MDBP) and three regioisomeric ring-substituted methoxybenzoylpiperazines (OMeBzPs) have identical elemental composition and no marked differences in their mass spectra with only the three methoxybenzoylpiperazine regioisomers showing one unique major fragment ion at m/z 152. 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. Exact mass determination using gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) did not provide any discrimination among these compounds since the main fragment ions are of identical elemental composition. 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 psychoactive designer drug 3,4-MDBP from its direct (2,3-MDBP) and indirect (OMeBzPs) regioisomers. The mass spectra in combination with the vapour phase infrared spectra provide for specific confirmation of each of the isomeric piperazines. The underivatized and perfluoroacyl derivative forms of the five piperazines involved in this study were resolved on a stationary phase of 100% trifluoropropyl methyl polysiloxane (Rtx-200).

Differentiation of methylbenzylpiperazines (MBPs) and benzoylpiperazine (BNZP) using GC-MS and GC-IRD.

Three-ring substituted methylbenzylpiperazines (MBPs) and their isobaric benzoylpiperazine (BNZP) have equal mass and many common mass spectral fragment ions. The mass spectrum of BNZP yields a unique benzoyl-group containing fragment at m/z 122 and an additional major fragment at m/z 69 that allows its discrimination from the three MBP regioisomers. Perfluoroacylation of the secondary amine nitrogen of these isomeric piperazines gave mass spectra with differences in relative abundance of some fragment ions but acylation does not alter the fragmentation pathway and did not provide additional MS fragments of discrimination among these isomers. Gas chromatography coupled with infrared detection (GC-IRD) provides direct confirmatory data for the structural differentiation between the four isomers. The mass spectra in combination with the vapour phase IR spectra provide for specific confirmation of each of the isomeric piperazines. The underivatized and perfluoroacyl derivatives of these four piperazines were resolved on a stationary phase of 100% trifluoropropyl methyl polysiloxane (Rtx-200). Gas chromatography coupled with time-of-flight mass spectrometry provides an additional means of differentiating between the isobaric MBP and BNZP which have equivalent nominal masses but are different in their elemental composition and exact masses.

Differentiation of methylenedioxybenzylpiperazines and ethoxybenzylpiperazines by GC-IRD and GC-MS.

The substituted benzylpiperazines, 3,4-methylenedioxybenzylpiperazine, its regioisomer 2,3-methylenedioxybenzylpiperazine and three isobaric ring substituted ethoxybenzylpiperazines have equal mass and many common mass spectral fragment ions. The mass spectra of the three ethoxybenzylpiperazines yield a unique fragment at m/z 107 that allows the discrimination of the three ring substituted ethoxybenzylpiperazines from the two methylenedioxy isomers. Perfluoroacylation of the secondary amine nitrogen of these isomeric piperazines gave mass spectra with differences in relative abundance of some fragment ions, but acylation does not alter the fragmentation pathway and did not provide additional MS fragments of discrimination among these isomers. Gas chromatography coupled with infrared detection provides direct confirmatory data for the structural differentiation between the five isomers. The mass spectra in combination with the vapor phase infrared spectra provide for specific confirmation of each of the isomeric piperazines. The perfluoroacyl derivatives of the ring substituted benzylpiperazines were resolved on a stationary phase of 50% phenyl and 50% methylpolysiloxane. Gas chromatography coupled with time-of-flight mass spectrometric detection provides an additional means of differentiating between the isobaric compounds 3,4-methylenedioxybenzylpiperazine and 4-ethoxybenzylpiperazine, which have similar nominal masses but are different in their calculated exact masses.