Stability-indicating determination of trimetazidine dihydrochloride inthe presence of two of its related substances using a direct GC/MS method.

A novel, simple, direct, and selective stability- indicating GC/MS procedure was developed for the determination of the anti-ischemic drug trimetazidine dihydrochloride (TMZ) in the presence of two of its related substances (potential impurities), namely, 2,3,4-trimethoxybenzyl alcohol (T1) and 2,3,4-trimethoxybenzaldehyde (T2). The method involved resolution of the undeilvatized compounds using a 100% dimethylpolysiloxane (Rtx-1) capillary column, and MS detection was carried out in the electron-impact mode. The peaks of the three compounds eluted at retention times 11.

Studies on the formation of N-methylperfluoroalkylnitrile cations from perfluoroacylphenethylamines in electron ionisation mass spectrometry: unique marker ion fragments in methamphetamine analysis.

The mass spectra of the perfluoroacyl derivatives of methamphetamine show a unique and characteristic fragment ion identified as the N-methylperfluoroalkylnitrile cation (C(n)F(2n+1)CNCH(3))(+). This ion appears at various m/z values depending on the nature of the perfluoroacyl species and is generated via rearrangement of the perfluoroacyl immonium fragment formed by loss of the benzyl-radical from the molecular ion. Analogous ions have been described in the mass spectra of other methamphetamine-like side chain substances regardless of the aromatic ring substitution pattern.

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.

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.

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).

GC-MS and GC-IRD studies on the ring isomers of N-methyl-2-methoxyphenyl-3-butanamines (MPBA) related to 3,4-MDMA.

The mass spectra of the controlled substance 3,4-MDMA and its regioisomer 2,3-MDMA are characterized by an imine fragment base peak at m/z 58 and additional fragments at m/z 135/136 for the methylenedioxybenzyl cation and radical cation, respectively. Three positional ring methoxy isomers of N-methyl-2-(methoxyphenyl)-3-butanamine (MPBA) have an isobaric relationship to 2,3- and 3,4-MDMA. All five compounds have the same molecular weight and produce similar EI mass spectra.

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.

GC-MS studies on side chain regioisomers related to substituted methylenedioxyphenethylamines: 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 forensic studies 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). A series of seven additional side chain regioisomers have mass spectra essentially equivalent to the three 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.

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.

GC-IRD methods for the identification of some tertiary amines related to MDMA.

Gas chromatography with infrared detection (GC-IRD) provides direct confirmatory data for the identification of the drug of abuse; 3,4-MDMA and its regioisomer; 2,3-MDMA, from a set of seven tertiary amines which have an isobaric or regioisomeric relationship with the MDMAs. These compounds include three ring substituted regioisomers of 2-dimethylamino-1-(methoxyphenyl)ethanone, two ring regioisomers of N,N-dimethyl-2-(methoxymethylphenyl)ethanamine in addition to N,N-dimethyl-2-(2,3- and 3,4-methylenedioxyphenyl)ethanamine. The major mass spectral fragments for each of these unique isomers occur at equivalent mass and all have equal molecular weight.

Stability-indicating simultaneous determination of paracetamol and three of its related substances using a direct GC/MS method.

A simple, direct, and selective stability-indicating GC/MS procedure was developed for the simultaneous determination of paracetamol (PR) and three of its related substances: 4-aminophenol (4-AP), acetanilide (AD), and 4'-chloroacetanilide (4-CA). The method involved resolution of the underivatized compounds using a 100% dimethylpolysiloxane (Rtx-1) column, and MS detection was carried out in the electron-impact mode. The four compounds were completely resolved in less than 11 min.

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.

Determination of paracetamol and tramadol hydrochloride in pharmaceutical mixture using HPLC and GC-MS.

Two simple, rapid, and selective analytical procedures were developed for the simultaneous determination of paracetamol (PR) and tramadol hydrochloride (TR) in a binary mixture using high-performance liquid chromatography with UV detection (HPLC-UV) and gas chromatography with mass spectrometry (GC-MS) techniques. HPLC resolved the two compounds on a Hypurity Advance column using a mobile phase consisting of phosphate buffer pH 6.3 and acetonitrile (90:10, v/v).

GC-IRD studies on regioisomeric ring substituted methoxy methyl phenylacetones related to 3,4-methylenedioxyphenylacetone.

The methoxy methyl phenylacetones share an isobaric relationship (equivalent mass but different elemental composition) to the controlled precursor substance 3,4-methylenedioxyphenylacetone (3,4-methylenedioxyphenyl-2-propanone; 3,4-MDP-2-P). The ten ring substituted methoxy methyl phenylacetones are resolved by capillary gas chromatography on a modified cyclodextrin stationary phase. All ten regioisomeric ketones eluted before the controlled precursor substance 3,4-methylenedioxyphenylacetone.

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.

GC-MS evaluation of a series of acylated derivatives of 3,4-methylenedioxymethamphetamine.

A series of acylated derivatives of 3,4-methylenedioxy-methamphetamine (3,4-MDMA) are prepared and evaluated in gas chromatography-mass spectrometry (GC-MS) studies. The perfluoroalkyl amides of 3,4-MDMA show the lowest GC retention, while the aromatic amides such as the benzamide show the greatest retention on the dimethylpolysiloxane stationary phase (Rtx-1). The mass spectral properties of the acetyl, propionyl, and butyryl derivatives all show a base peak at m/z 58 which is the base peak for the underivatized 3,4-MDMA.

GC and mass spectral studies on acylated side chain regioisomers of 3-methoxy-4-methyl-phenethylamine and 4-methoxy-3-methyl-phenethylamine.

The side chain regioiomers of the 3-methoxy-4-methylphenethylamines and 4-methoxy-3-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. Furthermore, the compounds in this study have ring substitutions in the same relative positions as 3,4-MDMA. The nonequivalence of the substituents (methoxy and methyl) yields two sets of compounds, 3-methoxy-4-methyl- and 4-methoxy-3-methylphenethylamines.

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.

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.

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.

GC-MS studies on the regioisomeric methoxy-methyl-phenethylamines related to 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 forensic studies 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). The mass spectra of the regioisomers (4-methoxy-3-methyl and 4-methoxy-2-methyl-phenethylamines) are essentially equivalent to the three compounds reported as drugs of abuse.

GC-MS analysis of ring and side chain regioisomers of ethoxyphenethylamines.

Mass spectral differentiation of 3,4-methylenedioxymethamphetamine (3,4-MDMA), a controlled drug, and its 2,3-regioisomer from the ring substituted ethoxyphenethylamines is possible after formation of the perfluoroacyl derivatives, pentafluoropropionamides (PFPA), and heptafluorobutyrylamides (HFBA). The ring substituted ethoxyphenethylamines constitute a unique set of compounds having an isobaric relationship with 3,4-MDMA. These isomeric forms of the 2-, 3-, and 4-ethoxy phenethylamines have mass spectra essentially equivalent to 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.

GC-MS analysis of acylated derivatives of a series of side chain regioisomers of 2-methoxy-4-methyl-phenethylamines.

Five side chain regioisomers of 2-methoxy-4-methylphenethylamine constitute a unique set of compounds having an isobaric relationship with the controlled drug substance 3,4-methylenedioxymethamphetamine (3,4-MDMA or Ecstasy). These isomeric forms of the 2-methoxy-4-methyl-phenethylamines have mass spectra essentially equivalent to 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. Mass spectral differentiation of 2,3 and 3,4-MDMA from primary and secondary amine regioisomeric side chains of 2-methoxy-4-methyl-phenethylamines was possible after formation of the perfluoroacyl derivatives, pentafluoropropionamides (PFPA) and heptafluorobutyrylamides (HFBA).

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.

GC-MS analysis of acylated derivatives of the side-chain regioisomers of 4-methoxy-3-methyl-phenethylamines related to methylenedioxymethamphetamine.

The five side-chain regioisomers of 4-methoxy-3-methylphenethylamine constitute a unique set of compounds having an isobaric relationship with the controlled drug substance 3,4-methylenedioxymethamphetamine (3,4-MDMA or Ecstasy). These isomeric forms of the 4-methoxy-3-methylphenethylamines have mass spectra essentially equivalent to 3,4-MDMA, and all have a molecular weight of 193 and major fragment ions in their electron ionization mass spectra at m/z 58 and 135/136. Mass spectral differentiation of 2,3- and 3,4-MDMA from primary and secondary amine regioisomeric side chains of 4-methoxy-3-methylphenethylamines was possible after formation of the perfluoroacyl derivatives, pentafluoropropionamides and heptafluorobutyrylamides.