Ethylamphetamine Research Articles

The Vaporization Enthalpy and Vapor Pressure of (±) N-Ethyl Amphetamine by Correlation Gas Chromatography.

The vaporization enthalpy, and vapor pressure as a function of temperature of N-ethylamphetamine, a substance used in the 1950s as an appetite suppressant and more currently abused as a designer drug, is reported. Its physical properties are compared to those of S (+)-N-methamphetamine, a substance whose physiological properties it mimics. A vaporization enthalpy of (62.4 ± 4.4) kJ·mol−1 and vapor pressure of (19 ± 11) Pa at T = 298.15 K has been evaluated by correlation gas chromatography. Results are compared to estimated values and to the limited amount of experimental property data available.

Impurity profiling of methamphetamine hydrochloride drugs seized in the Philippines

Methamphetamine hydrochloride is one of the most widely used illicit drugs in the Philippines. In this study, we describe the application of cluster analysis of trace impurities in the profiling of the seized methamphetamine drug samples. Thirty milligrams of a homogenized drug sample were dissolved in 1 mL of pH 10.5 buffer solution and extracted with ethyl acetate containing three internal standards. The trace impurities were identified using gas chromatography–mass spectrometry (GC–MS) and quantified by gas chromatography with a flame ionization detector (GC–FID). Following previously reported methodologies, 30 impurity peaks were selected from the GC–FID chromatograms. The peak areas and retention times were referenced to the internal standards. The peak areas of the selected peaks were then grouped for cluster analysis. In order to check for consistency of clustering, two further cluster analyses were performed using 40 and 50 impurity peaks. Changes in clustering were observed in going from 30 to 40 impurity peaks, while analyses using 40 and 50 impurity peaks gave similar results. Thus, for the seized drug samples used in this study, cluster analysis using at least 40 impurity peaks showed better consistency of clustering as compared to analysis using 30 peaks only. Ten of the impurity peaks were identified, of which four were identified for the first time in methamphetamine drug samples. These are p-bromotoluene, N-benzyl amphetamine, N-ethyl amphetamine, and N-ethyl methamphetamine. The presence of phenyl-2-propanone (P2P), N, N-dimethyl amphetamine, and N-formyl amphetamine is indicative that these casework samples were synthesized using the Leuckart method.

Involvement of CYP2D6 in the in vitro metabolism of amphetamine, two N-alkylamphetamines and their 4-methoxylated derivatives

1. Amphetamine (AM) and five amphetamine derivatives, N-ethylamphetamine (NEA), N-butylamphetamine (NBA), 4-methoxyamphetamine (M-AM), 4-methoxy-Nethylamphetamine (M-NEA) and 4-methoxy-N-butylamphetamine (M-NBA) were incubated with microsomal preparations from cells expressing human CYP2D6 to determine whether the enzyme was capable of catalyzing the direct ring oxidation of all substrates; the N-dealkylation of NEA, NBA, M-NEA and M-NBA; and the O-demethylation of M-AM, M-NEA and M-NBA. 2. None of the six compounds examined was N-dealkylated to any extent. 3. The only metabolites produced from AM, NEA and NBA were the corresponding ring 4-hydroxylated compounds, and the rates of formation were low. 4. All ring 4-methoxylated substrates were efficiently O-demethylated by CYP2D6 to their corresponding phenols. The size of the N-alkyl group influenced the rates of formation of these phenolamines. In contrast to reported findings with 2- and 3-methoxyamphetamines, none of the 4-methoxyamphetamines was ring-oxidized in the CYP2D6 enzyme system to 2- or 3-hydroxy-4-methoxyamphetamines or to dihydroxyamphetamines.

Gas Chromatography-Electron Ionization and Chemical Ionization Mass Spectrometric Analysis of Urinary Phenmetrazine After Derivatization with 4-Carbethoxyhexafluorobutyryl Chloride—A New Derivative

Phenmetrazine is a central nervous system stimulant currently used as an anorectic agent. The drug is abused and is reported to cause death from overdose. We describe a new derivatization method for phenmetrazine using 4-carbethoxyhexafluorobutyryl chloride. Quantitation of urinary phenmetrazine can be easily achieved by using N-ethyl amphetamine as an internal standard. The electron ionization mass spectrum of 4-carbethoxyhexafluorobutyryl derivative of phenmetrazine showed a molecular ion at m/z 427 and a base peak at m/z 70. In the methane chemical ionization mass spectrum, the base peak was observed at m/z 428 (protonated molecular ion). In the electron ionization mass spectrum of 4-carbethoxyhexafluorobutyryl derivative of the internal standard, N-ethyl amphetamine we did not observe a molecular ion. However, in the chemical ionization mass spectrum, the protonated molecular ion at m/z 414 was the base peak. The retention time of derivatized phenmetrazine (8.4 min) was substantially longer than the retention time of the underivatized molecule. Moreover, underivatized phenmetrazine showed poor peak shape (substantial tailing) while derivatized phenmetrazine had excellent chromatographic properties. The within-run and between-run precisions of the assay were 2.6% and 3.1% respectively at a urinary phenmetrazine concentration of 10 micrograms/mL. The assay was linear for urinary phenmetrazine concentration of 1 to 100 micrograms/mL with a detection limit of 0.2 microgram/mL.

Time-lapse changes of d- and l-enantiomers of racemic (dl)-ethylamphetamine in human urine.

The time-lapse changes of d- and i-forms in urine specimens collected in the 24 h after the oral dosing of two adult male subjects with 20 mg of racemic (dl)-ethylamphetamine (EAMP)-HCl were examined by high-performance liquid chromatography. The percentage of the excreted dose of nonmetabolized l-EAMP was larger than that of d-EAMP, and the percentage of the excreted dose of metabolized l-amphetamine (AMP) was smaller than that of d-AMP in both subjects, A and B. These differences were observed 4.5-24 h after administration of the drug. The changes in the l/d ratio of EAMP and AMP were not similar between subjects A and B, but the change in the total l/d ratio was nearly the same. The regression line for subject A was as follows: y = 0.021323x + 0.98399. The regression line for subject B was as follows: y = 0.020947x + 0.94893. These two regression lines suggested that the time lapsed after the administration to humans could be predicted. The total percent of the excreted doses of EAMP and AMP was 47.46% (the d-forms, 20.73%; the l-forms, 26.73%) for subject A and was 31.43% (the d-forms, 14.14%; the l-forms, 17.29%) for subject B. The l/d ratio was 1.29 for subject A and 1.22 for subject B, which was somewhat higher than that (1.01) of the dl-EAMP-HCl used.

Comparison of Mass Spectrometric Ionization Techniques for the Analysis of Phenethylamines

It is predicted that lower limits of detection can be obtained for some amphetamines—3,4(methylenedioxy)amphetamine (MDA), 3,4-(methylenedioxy)methylamphetamine (MDMA), and 3,4(methylenedioxy)-N-ethyl amphetamine (MDEA)—with the use of liquid chromatography coupled to mass spectrometry by thermospray, electrospray, and atmospheric pressure chemical ionization interfaces. The lowest detection limits are obtained with the thermospray interface; when a tandem mass spectrometric selected reaction monitoring technique is used in the product ion mode, the limits of detection are in the low picogram range for the amphetamines.

Analytical Method for N-Ethyl-3,4-methylenedioxyamphetamine.

The analytical method for N-ethyl-3, 4-methylenedioxyamphetamine (EMDA), one of the hallucinogenic phenethylamine derivatives newly controlled in Japan, was investigated in several aspects of forensic chemical analysis. The standard EMDA was synthesized from piperonylmethylketone. We analyzed EMDA, its related compounds (3, 4-methylenedioxymethamphetamine (MDMA), 3, 4-methylenedioxyamphetamine (MDA) and ethylamphetamine (EA)) and a seized sample containing EMDA, methamphetamine and caffeine using color test, thin-layer chromatography (TLC), infrared spectrometry (IR), gas chromatography (GC) and gas chromatographymass spectrometry (GC-MS). Under the analytical conditions described here, we succeeded in complete separation and identification of these drugs. It may also be possible to apply our method for the intake of drug abuse such as EMDA.

Structure-activity relationships among some d-N-alkylated amphetamines.

d-N-Alkylated amphetamines were synthesized in a series up to and including d-N-butylamphetamine and potencies of these compounds were compared in (1) rhesus monkeys allowed to respond for intravenous infusions of the drugs, (2) rats allowed to drink a milk solution for 15 minutes each day and (3) isolated, spontaneously beating guinea-pig atria. In the self-administration procedure, d-amphetamine (A), d-N-methylamphetamine (NMA), and d-N-ethylamphetamine (NEA) were self-administered above saline levels at two or more doses by all animals. For these three drugs, maximal response rates were found at similar doses in all animals. However, maximal rates were generally higher in animals maintained on pentobarbital than in animals maintained on cocaine under control conditions. d-N-propylamphetamine (NPA) was self-administered above saline levels by three of four animals at one or more doses. Maximal response rates for NPA were about 1/2 of that of A, NMA and NEA, and the dose-response curve was shifted to the right of these compounds by about 4 times. d-N-butylamphetamine (NBA) maintained responding above saline levels at two doses in only one of three animals. In rats, all of the compounds decreased milk intake in a dose-related manner. A, NMA and NEA were equipotent in disrupting intake, while NPA and NBA were, respectively, 1/4 and 1/6 as potent as the shorter-chain compounds. With the exception of NBA, all compounds increased the rate of beating of the guinea-pig atrium over the range of concentrations tested. In general, for substituents larger than ethyl, potency of d-N-alkylated amphetamines was inversely related to N-alkyl length.

The stereoselective metabolism of ethylamphetamine with fortified rabbit liver homogenates.

1. The liver enzyme systems of rabbits involved in the oxidative metabolism of ethylamphetamine were shown to be localized in the microsomal fraction. 2. The effect of substrate concentration, incubation period and storage of the microsomal preparations at 4 degrees was investigated. 3. The results indicate the involvement of at least two stereoselective enzyme systems or different conformations of binding of different substrates to the same enzyme system. R-(-)-Ethylamphetamine is the preferred substrate for N-oxidation and dealkylation, whereas the S-(+)-isomer is preferred for deamination. When racemic ethyl amphetamine is metabolized, the enantiomers act as independent compounds and compete for the enzymes. 4. Neither alpha-C- nor N-oxidation is induced by pre-treatment with phenobarbitone or 3-methylcholanthrene.