Chromatographic and mass spectral methods of identification for the side-chain and ring regioisomers of methylenedioxymethamphetamine.

The popular drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) is one of a total of 10 regioisomeric 2,3- and 3,4-methylenedioxyphenethylamines of MW 193 that yields regioisomeric fragment ions with equivalent mass (m/z 58 and 135/136) in the electron-impact (EI) mass spectrum. Thus, these 10 methylenedioxyphenethylamines are uniquely isomeric; they have the same molecular weight and equivalent major fragments in their mass spectra. The specific identification of one of these compounds (i.e., Ecstasy or 3,4-MDMA) in a forensic drug sample depends upon the analyst's ability to eliminate the other regioisomers as possible interfering or coeluting substances. This study reports the synthesis, chemical properties, spectral characterization, and chromatographic analysis of these 10 unique regioisomers. The ten 2,3- and 3,4-regioisomers of MDMA are synthesized from commercially available precursor chemicals. In the EI mass spectra, the side-chain regioisomers show some variation in the relative intensity of the major ions, with the exception of only one or two minor ions that might be considered side-chain specific fragments. The position of substitution for the methylenedioxy ring is not easily determined by mass spectral techniques, and the ultimate identification of any one of these amines with the elimination of the other nine must depend heavily upon chromatographic methods. The chromatographic separation of these 10 uniquely regioisomeric amines are studied using reversed-phase liquid chromatographic methods with gradient elution and gas chromatographic techniques with temperature program optimization.

GC-MS identification of amine-solvent condensation products formed during analysis of drugs of abuse.

The use of methanol or ethanol as the injection solvent for the gas chromatographic-mass spectral (GC-MS) analysis of low molecular weight amine drugs of abuse results in the formation of additional components in the sample. Primary amines, such as amphetamine, 3,4-methylenedioxyamphetamine, and phenethylamine, yield imines upon injection as methanol or ethanol solutions. In methanol, the imine formed has a mass that is 12 mass units higher than the parent compound. In ethanol, the products formed have 26 additional mass units. Secondary amines appear to undergo methylation under similar conditions with methanol as the injection solvent. These products are absent from the analysis of equivalent amine samples dissolved in chloroform.

Methods for the analysis of 1-(3,4-methylenedioxyphenyl)-2-butanamine and N-methyl-1-(3,4-methylenedioxyphenyl)-2-propanamine (MDMA).

The infrared and mass spectra of N-methyl-1-(3,4-methylenedioxyphenyl)-2-propanamine (MDMA) and 1-(3,4-methylenedioxyphenyl)-2-butanamine are quite similar. These two compounds differ only in the position of substitution of a single methyl group. MDMA is a controlled street drug known as Ecstasy, while the isomeric butanamine is a member of a new class of potential psychotherapeutic agents called entactogens. These two compounds produce similar mass spectral fragmentation patterns including a common base peak at m/z 58. Reversed-phase liquid chromatographic (RPLC) methods consisting of a C18 stationary phase and an aqueous scidic mobile phase were used to separate these two compounds. Thus, LC methods can be used to differentiate MDMA from the isomeric butanamine for forensic analysis.

Liquid chromatographic and mass spectral analysis of the anabolic 17-hydroxy steroid esters.

The liquid chromatographic separation of the common anabolic steroid esters is accomplished in an isocratic reversed-phase system. These anabolic steroids are now controlled substances in many states in the U.S. due to their potential for abuse and misuse. The esters are designed to be very lipophilic materials for slow release from intramuscular injection sites. With a C18 stationary phase material and a mobile phase of methanol-water (85:15), the more lipophilic esters such as testosterone decanoate show a retention time of about 50 min. These esters of varying lipophilicity are well resolved by reversed-phase liquid chromatography, and this technique is very useful for the identification of these compounds in forensic samples.

Liquid chromatographic and spectral analysis of the 17-hydroxy anabolic steroids.

The liquid chromatographic properties of various 17-hydroxy anabolic steroids are examined under reversed-phase conditions. These anabolic steroids are now listed as controlled drugs in many states due to their abuse potential in athletics, body building, and other areas. These nonesterified steroids are separated on a C18 stationary phase with a 70% methanol in water mobile phase. In a few cases, two compounds display very similar retention properties. However, dual-wavelength detection at 254 and 280 nm allows for their differentiation. Reversed-phase retention parallels steroid lipophilicity based on hydroxyl and methyl group substituents. Also, those steroids containing a dienone substructure are more polar than steroids containing an enone moiety.

Liquid chromatographic and mass spectral analysis of 1-(3,4-methylenedioxyphenyl)-1-propanamines: regioisomers of the 3,4-methylenedioxyamphetamines.

The title 1-(3,4-methylenedioxyphenyl)-1-propanamines represent positional isomers of the N-substituted 3,4-methylenedioxyamphetamines, clandestinely produced drugs frequently encountered by forensic laboratories. These propanamines are prepared by reductive amination of 3,4-methylenedioxypropiophenone with a series of N-alkylamines. Analytical methods are developed to distinguish these compounds from the MDA series. The ultraviolet spectra of the propanamines are very similar to those of the MDAs with absorption maxima at 284 and 236 nm. The propanamines are separated under reversed-phase liquid chromatographic conditions by using a C18 stationary phase and a mobile phase of acidic (pH 3) acetonitrile containing methanol and triethylamine. The relative retention properties of these compounds parallel those observed in the MDA series. The electron impact mass spectra of the propanamines are determined by GC-MS, and the fragmentation pattern clearly distinguishes these compounds from those of the MDA series having the same molecular weight.

Liquid chromatographic and mass spectral analysis of 1-(3,4-methylenedioxyphenyl)-3-butanamines, homologues of 3,4-methylenedioxyamphetamines.

The 1-(3,4-methylenedioxyphenyl)-3-butanamines (HMDAs) are prepared via reductive amination of the corresponding ketone with a series of low molecular weight alkylamines. These amines are homologues of the N-substituted 3,4-methylenedioxyamphetamines (MDAs). Compounds of the HMDA series have UV absorption properties similar to the MDAs because both series contain the same 3,4-methylenedioxyphenyl chromophore. The HMDAs are separated via reversed-phase liquid chromatographic methods using a C18 stationary phase and an acidic aqueous acetonitrile mobile phase. The mass spectra of these potential designer drugs are very similar to the spectra of the MDA homologues having the same N-substituent.

Liquid chromatographic and mass spectral analysis of N-substituted analogues of 3,4-methylenedioxyamphetamine.

The C1 to C3 N-alkyl, N,N-dimethyl, and N-hydroxy analogues of 3,4-methylenedioxyamphetamine (MDA) are identified by high performance liquid chromatographic (HPLC) and spectrometric techniques. The compounds are separated using reversed-phase procedures on C18 stationary phase with an acidic (pH 3) aqueous methanol mobile phase. The mass spectra of the compounds are distinctive and reference spectra are provided. The N-hydroxy derivative is unstable at high temperatures and decomposes to MDA and the oxime of 3,4-methylenedioxyphenyl-2-propanone.

Synthesis, identification, and acute toxicity of some N-alkyl derivatives of 3,4-methylenedioxyamphetamine.

A series of N-alkyl derivatives of 3,4-methylenedioxyamphetamine (MDA) was prepared in an effort to characterize these potential drugs of abuse. These secondary amines were synthesized via reductive amination of the corresponding ketone with alkylamines. The ultraviolet absorption spectra for these compounds produced almost equally intense absorbance at 234 and 285 nm. The compounds were separated by liquid chromatography using reverse phase (C18) procedures with a ternary mobile phase mixture. Toxicity studies showed all of the compounds to have LD50 values similar to N-methyl MDA (MDMA).

Liquid chromatographic determination of the enantiomeric composition of amphetamine prepared from norephedrine and norpseudoephedrine.

The stereochemical course of the synthesis of amphetamine from norephedrine and norpseudoephedrine is investigated using liquid chromatography. The results show that the chiral carbon common to both compounds remains unaffected during the reaction sequence. The presence of individual amphetamine enantiomers in the reaction products is determined by reversed-phase liquid chromatographic separation on an achiral stationary phase (C18) following precolumn derivatization with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (GITC). The GITC derivatization procedure allows for the liquid chromatographic separation of the individual enantiomers of amphetamine, norephedrine, norpseudoephedrine, and the intermediate 1-chloro-1-phenyl-2-aminopropanes.

Spectrophotometric and liquid chromatographic identification of 3,4-methylenedioxyphenylisopropylamine and its N-methyl and N-ethyl homologs.

3,4-Methylenedioxyphenylisopropylamine (MDA) is an hallucinogenic drug that somewhat resembles lysergic acid diethylamide (LSD) in its effects. Recently, widespread abuse of the N-methyl homolog (MDMA) of MDA has led to federal control. This article reports on the synthesis of the N-ethyl homolog (MDEA) of MDA as well as spectrophotometric and chromatographic methods for identification of the 3 homologs.

Resolution of some enantiomeric amines of forensic interest by high-performance liquid chromatography.

The high-performance liquid chromatographic resolution of the enantiomers of amphetamine, methamphetamine, ephedrine, and pseudoephedrine is described. The sugar isothiocyanate, 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (GITC), is used as a chiral derivatizing agent, with chromatographic separations of the diastereomers formed with each amine made using a standard achiral C18 stationary phase.

Synthesis, identification, and acute toxicity of alpha-benzylphenethylamine and alpha-benzyl-N-methylphenethylamine. Contaminants in clandestine preparation of amphetamine and methamphetamine.

Amphetamine samples obtained from clandestine laboratories often contain other by-product amines. The most common of these are the alpha-benzylphenethylamine derivatives. This article reports the independent synthesis of reference samples of these amines, spectrophotometric and chromatographic methods for their identification, as well as acute toxicological studies. The utility of the analytical methods is demonstrated by the analysis of several amphetamine samples containing these alpha-benzylphenethylamines.

Liquid chromatographic analysis of samples containing cocaine, local anesthetics, and other amines.

A liquid chromatographic procedure is described for the separation of cocaine, local anesthetics, and other amines often encountered in cocaine look-alike preparations. Amines such as ephedrine, pseudoephedrine, and phenylpropanolamine are identified following derivatization with phenylisothiocyanate. The isocratic, reverse phase method uses dual wavelength detection at 254 and 280 nm.

Liquid chromatographic identification of cis- and trans-cinnamoylcocaine in illicit cocaine.

A liquid chromatographic procedure is described for the analysis of illicit cocaine samples. The isomeric cis- and trans-cinnamoylcocaines are separated from cocaine, benzoylecgonine, and benzoic acid in a reverse phase isocratic system with dual wavelength detection at 254 and 280 nm. Specific identification of cocaine and the cinnamoylcocaines is accomplished by ultraviolet spectrophotometry and mass spectrometry of the chromatographic effluent.

Identification of some benzodiazepines of forensic interest.

Ten benzodiazepines--clorazepate, nitrazepam, clonazepam, oxazepam, lorazepam, chlordiazepoxide, N-desmethyldiazepam, diazepam, prazepam, and flurazepam--in solid dosage form are identified by ultraviolet (UV) and infrared (IR) spectrophotometry and by high pressure liquid chromatography (HPLC). UV absorption data and IR spectra of the 10 benzodiazepines are provided and HPLC separation methods are described.