Methamphetamine Synthesis Research Articles

Surface Contamination Generated by "One-Pot" Methamphetamine Production.

Methamphetamine production is the most common form of illicit drug manufacture in the United States. The "one-pot" method is the most prevalent methamphetamine synthesis method and is a modified Birch reduction, reducing pseudoephedrine with lithium and ammonia gas generated in situ. This research examined the amount of methamphetamine surface contamination generated by one-pot syntheses or "cooks", as well as the effectiveness of hosing with water as a simplified decontamination technique, to assess associated public health and environmental consequences. Concentrations of methamphetamine contamination were examined prior to production, after production, and after decontamination with water. Contamination was qualitatively field screened using lateral flow immunoassays and quantitatively assessed using a fluorescence covalent microbead immunosorbent assay. Following screening, 0 of 23 pre-cook samples, 29 of 41 post-cook samples, and 5 of 27 post-decontamination samples were positive. Quantitatively, one pre-cook sample had a methamphetamine concentration of 1.36 ng/100 cm2. Post-cook and post-decontamination samples had average methamphetamine concentrations of 26.50 ± 63.83 and 6.22 ± 12.17 ng/100 cm2, respectively. While all one-pot methamphetamine laboratories generate different amounts of waste, depending on the amount of precursors used and whether the reaction vessel remained uncompromised, this study examined the surface contamination generated by a popular one-pot method known to law enforcement. By understanding the amount of surface contamination generated by common methods of one-pot methamphetamine production and the effectiveness of decontamination techniques used to remediate them, health risks associated with these production sites can be better understood and environmental contamination can be mitigated.

Stereoselective analysis of ephedrine and its stereoisomers as impurities and/or by-products in seized methamphetamine by supercritical fluid chromatography/tandem mass spectrometry

In forensic science, drug profiling is clarifying the identity of seized drugs of abuse based on their physicochemical properties and it is applied to various drugs, including crystalline methamphetamine. Impurity analysis is particularly important in drug profiling because the impurities can be a measure for speculating how the methamphetamine was synthesized in the clandestine laboratories. However, developments in scientific techniques have allowed the synthesis of high-purity, homogeneous crystalline methamphetamine, and thus new techniques to characterize methamphetamine are needed. In this study, we developed a method for chiral separation of ephedrine and its stereoisomers by supercritical fluid chromatography. Ephedrine is a common starting compound for methamphetamine synthesis. It possesses two chiral center carbon atoms and has four stereoisomers, (1R,2S)–(−)–ephedrine, (1S,2R)–(+)–ephedrine, (1S,2S)–(+)–pseudoephedrine, and (1R,2R)–(−)–pseudoephedrine. Because the stereostructure of ephedrines contained in methamphetamine seizure reflects the starting materials and the synthetic pathways, the stereoisomer ratio will provide additional information for drug profiling. The developed method achieved rapid separation of four isomers in about 11min with low limits of detection (1pg on column). Due to a switching valve connecting a chromatograph to a mass spectrometer, dense methamphetamine sample solutions containing small amount of ephedrines could be analyzed directly with a simple pre-treatment. Using multivariate analysis, 44 real samples were objectively grouped based on stereoisomer ratio. Our method is expected to improve the profiling of crystalline methamphetamine.

Development of Methamphetamine Abuse–Deterrent Formulations Using Sucrose Acetate Isobutyrate

The objective of the present research was to investigate application of sucrose acetate isobutyrate (SAIB) in the development of a meth-deterrent formulation in combination with polyethylene oxide (PolyoxTM) and hydroxypropyl methylcellulose. The formulations were prepared by granulating pseudoephedrine hydrochloride, hydroxypropyl methylcellulose, and PolyoxTM with an ethanolic solution of SAIB and compressed into tablets followed by heat curing. The tablets were characterized for surface morphology, crystallinity, drug distribution, hardness, particle size, extraction, and dissolution. Hardness increased insignificantly, surface morphology indicated cracking and crevices, and diffractograms showed an increase and a decrease in drug and PolyoxTM crystallinity, respectively, after heat curing. Pseudoephedrine hydrochloride, PolyoxTM, and SAIB distribution was uniform as indicated by near infrared image. The drug extraction varied from 69.5% to 77.8%, 90.3% to 106.5%, 51.3% to 81.2%, and 48.9% to 72.6% in water, ethanol, 0.1 N HCl, and 0.1 N NaOH, respectively. The dissolution was more than 85% in 9 h from all the formulations. Thus, the addition of SAIB to the formulation decreased the drug extraction in various solvents which has the potential to decrease abuse of pseudoephedrine formulation for methamphetamine synthesis.

Potential for the Remediation of Methamphetamine Contamination Using Ozone.

The deposition of methamphetamine within indoor environments due to illegal activities can pose a health risk for occupants. Current cleaning techniques are costly and inefficient, calling for the development of alternative remediation methods. In addition, the fate of methamphetamine in indoor environments is largely unknown, negatively impacting our knowledge on the health risks associated with contaminated dwellings. Under the conditions of this study, 97% of surface deposited methamphetamine on a paper substrate was consumed after 12min of exposure to ozone, thus demonstrating potential for its use as a remediation agent. The reaction had an effective second-order rate constant with an upper limit of 2.15±1×10-18 cm3 /molecule/s, and the main product observed was phenyl-2-propanone (P2P) at 8.3% yield, as determined using GC/MS. Several products observed in this study have also been reported as by-products of methamphetamine synthesis, including P2P-a known methamphetamine precursor, which indicates that their detection at a potential clandestine site is not necessarily evidence of manufacture.

Chromatographic separation of R/S-enantiomers of amphetamine and methamphetamine: Pathways of methamphetamine synthesis and detection in blood samples by qualitative enantioselective LC–MS/MS analysis

Methamphetamine can be synthesized either enantiopure or in its racemic form. We separated (R)- and (S)-enantiomers of methamphetamine and amphetamine by a fast LC–MS/MS-method using a Lux® 3μm AMP 150×3.0mm analytical column after simple protein precipitation with methanol. Sufficient resolution could be achieved. Method validation for qualitative detection showed limits of quantification <5ng/mL while only little (maximum 14.5%) ion suppression could be shown. Stability in the processed sample could be achieved using isotopically labelled internal standards. Plasma samples of police cases from the german regions of Franconia and Northrhine revealed that in the majority of 106 tested samples (>99%) only (S)-methamphetamine was detected which leads to the conclusion that, in Germany, predominantly enantiopure (S)-methamphetamine is consumed which is synthesized via (1R,2S)-ephedrine or (1S,2S)-pseudoephedrine. However, racemic methamphetamine seems also to be on the market.

Enantiomeric profiling of chiral illicit drugs in a pan-European study

The aim of this paper is to present the first study on spatial and temporal variation in the enantiomeric profile of chiral drugs in eight European cities. Wastewater-based epidemiology (WBE) and enantioselective analysis were combined to evaluate trends in illicit drug use in the context of their consumption vs direct disposal as well as their synthetic production routes. Spatial variations in amphetamine loads were observed with higher use in Northern European cities. Enantioselective analysis showed a general enrichment of amphetamine with the R-(−)-enantiomer in wastewater indicating its abuse. High loads of racemic methamphetamine were detected in Oslo (EF = 0.49 ± 0.02). This is in contrast to other European cities where S-(+)-methamphetamine was the predominant enantiomer. This indicates different methods of methamphetamine synthesis and/or trafficking routes in Oslo, compared with the other cities tested. An enrichment of MDMA with the R-(−)-enantiomer was observed in European wastewaters indicating MDMA consumption rather than disposal of unused drug. MDA's chiral signature indicated its enrichment with the S-(+)-enantiomer, which confirms its origin from MDMA metabolism in humans. HMMA was also detected at quantifiable concentrations in wastewater and was found to be a suitable biomarker for MDMA consumption. Mephedrone was only detected in wastewater from the United Kingdom with population-normalised loads up to 47.7 mg 1000 people−1 day−1. The enrichment of mephedrone in the R-(+)-enantiomer in wastewater suggests stereoselective metabolism in humans, hence consumption, rather than direct disposal of the drug. The investigation of drug precursors, such as ephedrine, showed that their presence was reasonably ascribed to their medical use.

A survey on high-risk behaviors and HIV infection among men having sex with men who use drugs in Tianjin in 2016

Objective: To analyze the characteristics of high risk sexual behaviors and HIV infectious status among men who have sex with men (MSM) who use drugs in Tianjin in 2016. Methods: From April to December in 2016, MSM who use drugs in Tianjin were targetedly and extensively mobilized to receive testing by snowball sampling method. The inclusion criteria were as follows: men aged 18 years old and above; have had oral or anal sex with men in the last 6 months; have had drug abuse history in the last 6 months, including the use of rush poppers, 5-Methoxy-diisopropyltryptamine (5-MeO-DiPT), and Methamphetamine Synthesis substances; and with no mental disorder or mental deficiency. In this study, 302 MSMs were recruited to collect information of social demographic characteristics, drug abuse situation, sexual behavior after drug use, HIV test and the infectious status was collected through the online questionnaire, and the descriptive analysis was conducted. Results: From January to December 2016, a total of 302 subjects were recruited, among whom 194 (64.2%) aged 21-30 years old, 223 (73.8%) were unmarried and 28 (9.3%) were students. In the past 6 months, 297 (98.3%) used rush poppers, 31 (10.3%) used 5-MeO-DiPT, and 14(4.6%) used Methamphetamine Synthesis substances. The proportion of having sex after using the three types of drugs were 87.9% (n=261), 83.9% (n=26) and 92.9% (n=13), 85.5% (n=254), 87.1% (n=27) and 92.9% (n=13) of the subjects reported the sexual pleasure and sexual desire increased after using drugs, respectively. After using the three types of the drugs,58.6% (n=174), 83.9% (n=26) and 92.9% (n=13) of the subjects reported the duration of each sexual activity prolonged. In the past 3 months,48.3% (n=146) had stable sexual partners, 72.5% (n=219) had temporary sexual partners and 12.3% (n=37) had group sexual behaviors. 41 out of 302 subjects were HIV positive with the HIV positive rate at 13.6%. Conclusion: Most of the MSM who use drugs were young, and always had sex when they use drugs. There is a relatively high HIV prevalence in this population.

Theoretical calculations applied to the study of the energetics of reactions of methamphetamine synthesis and to the characterization of reactants, products and by-products

Abstract Density Functional Theory (DFT) was used to perform quantum chemical calculations at B3LYP level, with the 6-31G** basis set, as implemented by the Spartan computer program. The entities studied are the reaction of synthesis of MDMA (3,4, methylene dioxymethamphetamine), and a number of analogs of methamphetamine. The analogs have also been geometry-optimized and their infrared vibrational frequencies were calculated.

SPE?TLC Profiling of Impurities in 1-(3,4-Methylenedioxyphenyl)-2-nitropropene, an Intermediate in 3,4-Methylenedioxy- methamphetamine (MDMA) Synthesis

Impurity profiling of 1–(3,4-methylenedioxyphenyl)-2-nitropropene, an intermediate in the synthesis of 3,4-methylenedioxymethamphetamine (MDMA), has been studied by SPE combined with TLC. Extraction of impurities was performed on C18 columns. TLC separation was performed on 0.2 mm silica gel 60 plates, with fluorescent indicator F254, in a horizontal developing chamber. To improve the quality of the profile (increase the TLC sensitivity) SPE extracts were concentrated by evaporation in a stream of nitrogen. The usefulness of methanol, ethanol, ethyl acetate, chloroform, acetonitrile, and their mixtures as mobile phases was tested by use of Gibbs’s triangle. Spots of the separated impurities were observed under UV light (λexc=254 and 366 nm). The proposed characteristics of profile quality (optimization criteria) are based on matrix presentation of the TLC pattern. They take into account, simultaneously, the number of spots revealed, differences between RF values, and the intensity of fluorescence.

TLC Profiling of Impurities of 1‐(3,4‐Methylenedioxyphenyl)‐2‐nitropropene an Intermediate in MDMA Synthesis. Influence of Sample Preparation Methods and Conditions

Thin‐layer chromatography (TLC) was employed for screening profiling of impurities of 1‐(3,4‐methylenedioxyphenyl)‐2‐nitropropene, an intermediate product of (3,4‐methylenedioxy)methamphetamine (MDMA) synthesis (from piperonal). Liquid–liquid extraction (LLE) and solid phase extraction (SPE) were applied to isolate impurities from the drug matrix. The SPE extraction process was performed on C8 columns and LLE was carried out using n‐heptane. The influence of buffer solutions (pH 1, 4, 5, 6, 7, 8, 10, 11, 13, and 14) on the extraction efficiency was investigated. The chromatograms were developed with the use of chloroform:ethyl acetate (98:2) mixture. The spots of separated impurities were observed under UV light at λexc = 254 and 366 nm. The proposed semiquantitative criterion of profile (chromatogram) quality has been based on a matrix presentation of TLC patterns. It takes into account the number of spots revealed, differences between R f values, and intensity of fluorescence, simultaneously.

Chloroephedrine: contaminant of methamphetamine synthesis with cardiovascular activity

Chloroephedrine is an intermediate and possible contaminant formed when methamphetamine is manufactured using ephedrine or pseudoephedrine as precursors. The purpose of this study was to determine whether this contaminant has biological activity and might contribute to methamphetamine-induced cardiovascular toxicity. In conscious rats, the (−) and (+) isomers of chloroephedrine (0.1 and 1.0 mg/kg, i.v.) dose-dependently increased mean arterial pressure (MAP) and heart rate (HR). The potency of the pressor effects of (−) and (+)-chloroephedrine was between that of ephedrine and pseudoephedrine. The increases in HR elicited by the four stimulants were similar except that the tachycardia elicited by all doses of ephedrine and pseudoephedrine were preceded by a brief decrease in HR. The i.v. administration of 10 mg/kg of (+) or (−)-chloroephedrine produced biphasic (decrease followed by increase) the MAP and HR responses. Ephedrine and pseudoephedrine did not decrease MAP at any dose tested. The initial decrease in HR elicited by (−)-chloroephedrine was significantly reduced and the hypotensive response abolished by atropine, indicating that these components of the MAP and HR responses resulted from vagal activation. The secondary pressor response elicited by (−)-chloroephedrine was significantly reduced and the tachycardia significantly increased by pretreatment with phentolamine (3 mg/kg, i.v.). The increase in HR was reversed by propranolol. These results indicate that (−) and (+)-chloroephedrine have sympathomimetic properties similar to other known sympathomimetic stimulants. In addition, larger doses of chloroephedrine can activate the vagus nerve. The combination of (+)-methamphetamine and (−)-chloroephedrine did not markedly alter the magnitude of the MAP and HR responses of (+)-methamphetamine alone except at high doses of (−)-chloroephedrine (10 mg/kg). Contamination of illicit methamphetamine with chloroephedrine may have toxic consequences.

Nuclear forensics in law enforcement applications

Over the past several years, the Livermore Forensic Science Center has conducted analyses of nuclear-related samples in conjunction with domestic and international criminal investigations. Law enforcement officials have sought conventional and nuclear-forensic analyses of questioned specimens that have typically consisted of miscellaneous metal species or actinide salts. The investigated activities have included nuclear smuggling and the proliferation of alleged fissionable materials, nonradioactive hoaxes such as “Red Mercury,” and the interdiction of illegal laboratories engaged in methamphetamine synthesis.

Pharmacological characterization of BNMPA (α-benzyl- N-methylphenethylamine), an impurity of illicit methamphetamine synthesis

α-Benzyl- N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis, has previously been reported to produce convulsions in mice without affecting spontaneous locomotor activity or altering methamphetamine-induced increases in spontaneous activity. In this study the in vitro effects of BNMPA on a variety of neuronal receptor types was determined to better characterize the pharmacological actions of this novel compound. BNMPA and N-demethyl-BNMPA fully displaced the dopamine transporter selective ligand [ 3H]CFT (2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane) from rat striatal membranes with K i values (mean ± S.E.M) of 6.05 μM ± 0.15 and 8.73 μM ± 1.66, respectively. BNMPA also inhibited [ 3H]dopamine uptake into striatal synaptosomes with an IC 50 value of 5.1 ± 1.4 μM. The basal efflux of [ 3H]dopamine from striatal slices was slightly enhanced by BNMPA only at concentrations ≥ 100 μM. BNMPA had no effect on [ 3H]norepinephrine efflux from hippocampal slices. BNMPA displaced tritiated paroxetine and prazosin binding from rat cortical membranes with K i values of 14.5 μM and 11.7 μM respectively. In electrophysiological studies, BNMPA (100 μM) had no significant effects on either GABA A Cl − currents in cultured neurons or non-NMDA glutamate receptors expressed in oocytes. However, BNMPA significantly inhibited NMDA-stimulated currents in oocytes expressing the NR1/2A or NR1/2C receptor subunit combinations (IC 50 values = 24.6 ± 1.8 and 24.0 ± 1.5 μM, respectively). This inhibition was rapid, reversible and voltage-dependent. These results indicate that BNMPA has multiple sites of action in the CNS that could be important in modulating a variety of behavioral effects upon exposure to this synthetic byproduct of illicit methamphetamine synthesis.

The Detection of a Metabolite of α-Benzyl-N-methylphenethylamine Synthesis in a Mixed Drug Fatality Involving Methamphetamine

A 37-year-old, white male collapsed at his home following a party. He reportedly had a history of unspecified cardiac arrhythmia. The ambulance crew found him unresponsive and an ECG revealed ventricular tachycardia/fibrillation. Following one hour of resuscitative efforts in the ambulance and emergency room of a local hospital, he was pronounced dead. An antemortem urine toxicology screen performed at the hospital was "positive" for benzodiazepines, cocaine and amphetamine/methamphetamine. At autopsy, there was generalized organ congestion with no evidence of trauma or other significant pathology except mild, left ventricular hypertrophy. Quantitation by gas chromatography/mass spectrometry (GC/MS) of methamphetamine in bile, blood, urine and gastric contents yielded 21.7, 0.7, 32.0 and 2.9 mg/L, respectively. Liver and brain contained 2.2 and 2.7 mg/kg, respectively. A trace amount of p-OH-alpha-benzyl-N-methylphenethylamine (p-OH-BNMPA), a metabolite of alpha-benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis, was also detected in the urine. Since these impurities can be characteristic of a particular synthetic method, their presence in seized samples or their detection in biological samples from methamphetamine users can further be used to monitor the sales of precursor chemicals, group seized compounds to common sources of illicit production or provide links between manufacturers, dealers and users.

α-Benzyl-N-Methylphenethylamine (BNMPA), an Impurity of Illicit Methamphetamine Synthesis: III. Detection of BNMPA and Metabolites in Urine of Methamphetamine Users

Eighty urine specimens collected from drug rehabilitation programs, which had been screened by immunoassay and confirmed positive by gas chromatography-mass spectrometry (GC-MS) for methamphetamine, were further analyzed for alpha-benzyl-N-methylphenethylamine (BNMPA) and its urinary metabolites, N-demethyl-BNMPA, diphenyl-2-propanone (DP2P), diphenyl-2-propanol, p-OH-N-demethyl-BNMPA, and p-OH-BNMPA. BNMPA is an impurity of illicit methamphetamine synthesis. Analysis of BNMPA and its metabolites was performed by quantitative GC-MS following beta-glucuronidase hydrolysis, liquid-liquid extraction, and derivatization with heptafluorobutyric anhydride. Two urine specimens contained detectable amounts of BNMPA and/or its metabolites. One contained trace amounts (greater than the limit of detection but less than the limit of quantitation) of N-demethyl-BNMPA and DP2P, as well as 0.04 mg/L p-OH-N-demethyl-BNMPA. The other contained trace amounts of BNMPA, p-OH-BNMPA, and p-OH-N-demethyl-BNMPA, as well as 0.03 mg/L N-demethyl-BNMPA. Prior to analyzing these urine specimens, pure reference material of p-OH-BNMPA was made available, and analysis confirmed our previous tentative identification of p-OH-BNMPA as a major metabolite of BNMPA. Detection of BNMPA or its metabolites in biological samples may serve as a marker of illicit methamphetamine administration.

Alpha-Benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis: II. Metabolism and urinary excretion (human).

Methamphetamine is a popular drug of abuse, which is readily synthesized in clandestine laboratories. Illicit synthesis results in the formation of various contaminants. Few impurities have been studied in vivo, and their metabolic fate is unknown. One such impurity is alpha-benzyl-N-methylphenethylamine (BNMPA). The detection of BNMPA or its metabolites in urine samples may provide a marker of use of illicitly synthesized methamphetamine. Benzphetamine is structurally similar to BNMPA. Based on metabolic studies of benzphetamine, we predicted the four major metabolites of BNMPA to be the N-demethyl compound, diphenyl-2-propanone (DP2P), p-hydroxy-N-demethyl BNMPA, and p-hydroxy-BNMPA. One male volunteer ingested 5 mg BNMPA. Seventeen urine specimens were collected over 50 h post ingestion. These specimens were analyzed for BNMPA and its four predicted major metabolites by gas chromatography-mass spectrometry following beta-glucuronidase hydrolysis or acid hydrolysis, liquid-liquid extraction, and derivatization with heptafluorobutyric anhydride. Specimens were also analyzed without hydrolysis to determine the abundance of nonconjugated ("free") metabolites. Only trace amounts of BNMPA and its N-demethyl metabolites were detected, and maximum excretion was from 2 to 4 h post ingestion. In the nonhydrolyzed samples, the phenyl-OH metabolites were also present in only trace amounts. Maximum excretion of DP2P was at 2 h. Following either hydrolysis procedure, phenyl-OH-BNMPA and phenyl-OH-N-demethyl BNMPA were the major metabolites detected. Maximum excretion of these two metabolites occurred at 4 h. With the exception of the parent compound and the N-demethyl metabolite, excretion of metabolites was greater than the limit of detection of this procedure (2.5 ng/mL) up to 21 h post ingestion. Metabolites were detectable in sufficient quantities to serve as an adequate marker of illicit methamphetamine consumption within the preceding 24 h.

Alpha-Benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis: I. Physical characterization and GC-MS analysis of BNMPA and anticipated metabolites in urine.

alpha-Benzyl-N-methylphenethylamine (BNMPA) is an impurity of illicit methamphetamine synthesis. We synthesized BNMPA and three of its anticipated metabolites: N-demethyl-alpha-benzyl-phenethylamine, 1,3-diphenyl-2-propanone, and 1,3-diphenyl-2-propanol. The purity and structure of these compounds and their heptafluorobutyric anhydride (HFBA) derivatives were confirmed by melting point, gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance. A GC-MS method to detect these compounds in urine, using liquid-liquid extraction and derivatization with HFBA, was developed. Interference studies showed BNMPA and its proposed metabolites to be well-resolved from other common phenethylamine drugs and Health and Human Services-Forensic Urine Drug Testing required analytes. The limit of detection of BNMPA and its metabolites was 2.5 ng/mL; the limit of quantitation (LOQ) of the four compounds was 25 ng/mL. The calibration curves were generally linear from 25 to 500 ng/mL. Typical within-run coefficients of variation (CVs) at the LOQ ranged from 13 to 20% (n = 8). Between-run CVs over 1 month at 25 ng/mL were from 9 to 28%, and at 500 ng/mL, they were from 2.6 to 3.9%. The detection of BNMPA or its metabolites in urine samples may provide a marker of use of illicitly synthesized methamphetamine.

α-Benzyl- N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis: pharmacological evaluation and interaction with methamphetamine

Methamphetamine is a popular drug of abuse, readily synthesized in clandestine laboratories. Illicitly obtained methamphetamine is frequently impure, containing various purposefully added diluents and adulterants, as well as impurities of manufacture and origin. Few impurities have been studied in vivo and limited information exists concerning their pharmacology/toxicology. One such impurity of manufacture is α-benzyl- N-methylphenethylamine (BNMPA). Acute toxicity and spontaneous activity (locomotor) studies were conducted with this compound alone and in combination with S(+)-methamphetamine (METH) in male, ICR mice. In the acute toxicity studies, BNMPA was evaluated for convulsant activity. While BNMPA also produced some behavioral disturbances similar to those seen with methamphetamine (e.g., stereotopy) at doses greater than 30 mg/kg, no tonic-clonic convulsions were noted until pre-terminal convulsions at 50 mg/kg. METH alone produced tonic-clonic convulsions at terminal doses of 70 mg/kg. When BNMPA was given in combination with METH, there was no readily apparent change in the convulsion profile from that of METH given alone. In spontaneous activity studies, doses of BNMPA ranging from 1 mg/kg to 50 mg/kg failed to alter locomotor activity significantly from controls though 5 mg/kg METH alone significantly increased spontaneous activity. In addition, increases in spontaneous activity elicited by 5 mg/kg METH were not affected when METH was given with 5 mg/kg BNMPA. While BNMPA appears to have toxic effects in the central nervous system (CNS), the failure to affect locomotor activity or alter either METH-induced increases in spontaneous activity or METH-induced convulsions suggests that the two agents are producing their effects through distinct mechanisms.

Methamphetamine synthesis via reductive alkylation hydrogenolysis of phenyl-2-propanone with N-benzylmethylamine

Methamphetamine was synthesized by reductive alkylation hydrogenolysis of phenyl-2-propanone with N-benzylmethylamine. The expected product N-benzylmethamphetamine, once formed, undergoes hydrogenolysis to methamphetamine and toluene. The progress of the reaction, the intermediates formed during the reaction, and the products were analyzed by gas chromatography and mass spectrometry.

Methamphetamine synthesis via hydriodic acid/red phosphorus reduction of ephedrine

The illicit manufacture of methamphetamine from ephedrine via reduction with hydriodic acid and red phosphorus is discussed. The stereochemistry, mechanism, synthetic impurities, and analysis of clandestine methamphetamine samples are addressed.