Tamer Awad

GC-IRD methods for the identification of isomeric ethoxyphenethylamines and methoxymethcathinones

A series of 12 isomeric phenethylamines were evaluated by gas chromatography using vapor phase infrared spectrophotometric detection. The major mass spectral fragments for each of these unique isomers occur at equivalent mass and all have equal molecular weight. The infrared spectra for these compounds allow for identification of any one of these amines to the exclusion of all other isomers. This differentiation is accomplished without the need for chemical derivatization. The methoxymethcathinones show unique infrared absorption bands in the 1690-1700 cm(-1) range for the carbonyl group and the ring substitution pattern in the ethoxymethamphetamines can be differentiated by several bands in the 700-1610 cm(-1) region. Side chain and degree of nitrogen substitution can be evaluated in the 2770-3000 cm(-1) region of the infrared range. All the studied regioisomers could be differentiated from 3,4-MDMA via their vapor phase IR spectra. Capillary gas chromatography on an Rxi-50 stationary phase successfully resolved the side chain regioisomers, the substituted methamphetamines and the methoxymethcathinones.

Differentiation of the regioisomeric 2-, 3-, and 4-trifluoromethylphenylpiperazines (TFMPP) by GC–IRD and GC–MS

Gas chromatography with infrared detection (GC-IRD) provides direct confirmatory data for the identification of the psychoactive designer drug 3-trifluoromethylphenylpiperazine (3-TFMPP) from the regioisomeric 2- and 4-trifluoromethylphenylpiperazines. These three regioisomeric substances are well resolved by GC and the vapor phase infrared spectra clearly differentiate among the three trifluoromethylphenyl substitution patterns. However, the mass spectra for the three regioisomeric 2-, 3-, and 4-trifluoromethylphenylpiperazines are identical and do not provide structural confirmation for one of the three isomers to the exclusion of the other two compounds. Perfluoroacylation of the secondary amine nitrogen for each of the three regioisomers was conducted in an effort to individualize their mass spectra. The resulting derivatives were resolved by GC 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.

GC–MS studies on acylated derivatives of 3-methoxy-4-methyl- and 4-methoxy-3-methyl-phenethylamines: Regioisomers related to 3,4-MDMA

A series of side chain regioisomers of 3-methoxy-4-methyl- and 4-methoxy-4-methyl-phenethylamines have mass spectra essentially equivalent to the controlled drug substance 3,4-methylenedioxymethamphetamine (3,4-MDMA), all have molecular weight of 193 and major fragment ions in their electron ionization mass spectra at m/z 58 and 135/136. The acetyl, propionyl and trifluoroacetyl derivatives of the primary and secondary regioisomeric amines were prepared and evaluated in GC-MS studies. The mass spectra for these derivatives were significantly individualized and the resulting unique fragment ions allowed for specific side chain identification. The trifluoroacetyl derivatives provided more fragment ions for molecular individualization among these regioisomeric substances. These trifluoroacetyl derivatives showed excellent resolution on a non-polar stationary phase such as Rtx-1.

Comparison of GC–MS and GC–IRD methods for the differentiation of methamphetamine and regioisomeric substances

Gas chromatography-mass spectrometry (GC-MS) and gas chromatography-infrared detection (GC-IRD) methods were developed and compared for the differentiation of regioisomeric phenethylamines related to methamphetamine. There are a total of five regioisomeric phenethylamines (methamphetamine and four regioisomers) that produce essentially equivalent mass spectra. This unique set of five phenethylamines having the same molecular weight and elemental composition yield major mass spectral fragments at equivalent mass. The trifluoroacetyl derivatives of the primary and secondary amines yield characteristic individual fragment ions allowing structural differentiation among these regioisomers. The vapor phase infrared spectra generated via capillary gas chromatography differentiated among these compounds without the need for derivatization. The regioisomeric phenethylamines are well resolved by GC with the elution order generally determined by the degree of molecular linearity.

Differentiation of methylenedioxybenzylpiperazines (MDBP) by GC-IRD and GC-MS

The substituted benzylpiperazine, 3,4-methylenedioxybenzylpiperazine (3,4-MDBP) and its regioisomer 2,3-methylenedioxybenzylpiperazine (2,3-MDBP) have almost identical mass spectra. Perfluoroacylation of the secondary amine nitrogen of these regioisomeric piperazines gave mass spectra with differences in relative abundance of some fragment ions. However the spectra did not yield any unique fragments for specific identification of one regioisomer to the exclusion of the other compound. Gas chromatographic separation coupled with infrared detection (GC-IRD) provides direct confirmatory data for structural differentiation between the two regioisomers. The mass spectrum in combination with the vapor-phase infrared spectrum provides for specific confirmation of each of the regioisomeric piperazines. The underivatized and perfluoroacyl derivative forms of the ring substituted benzylpiperazines were resolved on a 30-m capillary column containing an Rxi-50 stationary phase.

GC-MS and GC-IRD studies on dimethoxyamphetamines (DMA): Regioisomers related to 2,5-DMA

The mass spectrum of the drug of abuse 2,5-dimethoxyamphetamine (2,5-DMA) is characterized by an imine fragment base peak at m/z 44 and additional fragments at m/z 151/152 for the dimethoxybenzyl cation and radical cation, respectively. Five positional ring isomers of dimethoxyamphetamines (DMA) have an isomeric relationship to 2,5-DMA. All six compounds have the same molecular weight and produce similar EI mass spectra. This lack of mass spectral specificity for the isomers in addition to the possibility of chromatographic coelution could result in misidentification. The lack of reference materials for the potential imposter molecules constitutes a significant analytical challenge. Perfluoroacylation of the amine group reduced the nitrogen basicity and provided individual fragmentation pathways for discrimination between these compounds based on some unique fragment ions and the relative abundance of common ions. GC-IRD studies provided additional structure-IR spectra relationships and yielded confirmation level identification for each of the six regioisomeric dimethoxyamphetamines. The amines and their perfluoroacylated derivatives were resolved by capillary gas chromatography and the amines showed excellent resolution on the more polar stationary phase, Rtx-200.

Differentiation of methylenedioxybenzylpiperazines (MDBPs) and methoxymethylbenzylpiperazines (MMBPs) By GC-IRD and GC-MS

The substituted benzylpiperazines, 3,4-methylenedioxybenzylpiperazine (3,4-MDBP), its regioisomer 2,3-methylenedioxybenzylpiperazine (2,3-MDBP) and four isobaric ring substituted methoxymethylbenzylpiperazines (MMBP) have almost identical mass spectra. Perfluoroacylation of the secondary amine nitrogen of these isomeric piperazines gave mass spectra with differences in relative abundance of some fragment ions. However, the spectra did not yield any unique fragments for specific identification of one isomer to the exclusion of the other compounds. Gas chromatography coupled with infrared detection (GC-IRD) provides direct confirmatory data for the structural differentiation between the six isomers. The mass spectra in combination with the vapor phase infrared spectra provide for specific confirmation of each of the isomeric piperazines. The underivatized and perfluoroacyl derivative forms of the ring substituted benzylpiperazines were resolved on the polar stationary phase Rtx-200.

GC-MS and GC-IRD studies on dimethoxyphenethylamines (DMPEA): regioisomers related to 2,5-DMPEA.

A series of regioisomeric dimethoxyphenethylamines have a mass spectra essentially equivalent to the drug substance 2,5-dimethoxyphenethylamine (2,5-DMPEA). These substances have a molecular weight of 181, and major fragment ions in their electron ionization mass spectra at m/z 151/152. The trifluoroacetyl, pentafluoropropionyl, and heptafluorobutryl derivatives of these primary amines were prepared and evaluated by gas chromatography with mass spectrometry detection (GC-MS). The mass spectra for these derivatives do not show unique fragment ions to allow the specific identification of a particular isomer. Thus, GC-MS does not provide for the confirmation of identity of any one of the six isomers to the exclusion of the other five compounds. However, GC-MS does divide the compounds into two groups depending on the mass of the base peak. GC with infrared detection provides direct confirmatory data for the identification of 2,5-DMPEA from the other regioisomers involved in the study. Perfluoroacylated derivatives of the six regioisomeric dimethoxyphenethylamines were successfully resolved via capillary GC on a non-polar stationary phase consisting of 50% phenyl and 50% methyl polysiloxane (Rxi-50).

GC-MS and GC-IRD analysis of ring and side chain regioisomers of ethoxyphenethylamines related to the controlled substances MDEA, MDMMA and MBDB

Three regioisomeric 3, 4-methylenedioxyphenethylamines having the same molecular weight and major mass spectral fragments of equal mass have been reported as drugs of abuse in recent years. These compounds are 3,4-methylenedioxy-N-ethylamphetamine (MDEA), 3,4-methylenedioxy-N,N-dimethylamphetamine (MDMMA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB). Ring substituted ethoxy phenethylamines having the same side chain are compounds with an isobaric relationship to these controlled drug substances, all have molecular weight of 207 and major fragment ions in their electron ionization mass spectra at m/z 72 and 135/136. The three methylenedioxyphenethylamines were resolved from the ethoxyphenethylamines by capillary gas chromatography using an Rxi-50 stationary phase. The trifluoroacetyl, pentafluoropropionyl and heptafluorobutryl derivatives of the secondary amines were evaluated in GC-MS studies. The mass spectra for these derivatives were significantly individualized and the resulting unique fragment ions allowed for specific side chain identification. The perfluoroacyl derivatives showed reasonable resolution on a non-polar stationary phase such as Rtx-1. GC-IRD studies provided structure-IR spectra relationships used for the discrimination of the three target drugs (MDEA, MDMMA and MBDB) from the other nine ring substituted ethoxyphenethylamine regioisomers.

GC-MS and GC-IRD studies on brominated dimethoxyamphetamines: regioisomers related to 4-Br-2,5-DMA (DOB).

A series of regioisomeric bromodimethoxyamphetamines have mass spectra essentially equivalent to the controlled drug substance 4-Br-2,5-dimethoxyamphetamine (4-Br-2,5-DMA; DOB); all have molecular weight of 274 and major fragment ions in their electron ionization mass spectra at m/z 44 and m/z 230/232. The trifluoroacetyl, pentafluoropropionyl and heptafluorobutryl derivatives of the primary regioisomeric amines were prepared and evaluated in gas chromatography-mass spectrometry (GC-MS) studies. The mass spectra for these derivatives did not show unique fragment ions for specific identification of individual isomers. However, the mass spectra do serve to divide the compounds into three groups, depending on their base peak. Gas chromatography with infrared detection (GC-IRD) provides direct confirmatory data for the identification of the designer drug 4-bromo-2,5-dimethoxyamphetamine from the other regioisomers involved in the study. The perfluoroacylated derivatives of the six regioisomeric bromodimethoxyamphetamines were successfully resolved on non-polar stationary phases such as a 100% dimethylpolysiloxane stationary phase (Rtx-1) and 50% phenyl - 50% methyl polysiloxane (Rxi-50).