N-Methyl Hallucinogenic Amphetamine Analysis

[methyl_ethyl]

Stereochemical analysis of 3,4-methylenedioxymethamphetamine and its main metabolites in human samples including the catechol-type metabolite (3,4-dihydroxymethamphetamine).
Pizarro N, Farre M, Pujadas M, Peiro AM, Roset PN, Joglar J, De La Torre R.
Drug Metab Dispos. 2004 Sep;32(9):1001-7.

Medline (PMID=15319342)

Abstract:

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a designer drug commonly misused in large segments of young populations. MDMA is usually formulated in tablets of its racemate (1:1 mixture of its enantiomers) in doses ranging from 50 to 200 mg. MDMA has an enantioselective metabolism, the (S)-enantiomer being metabolized faster than the (R)-enantiomer. Different pharmacologic properties have been attributed to each enantiomer. The carbon responsible for MDMA chirality is preserved along its metabolic disposition. An analytical method has been developed to determine MDMA enantiomers and those from its major metabolites, 3,4-methylenedioxyamphetamine (MDA), 3,4-dihydroxymeth-amphetamine (HHMA), and 4-hydroxy-3-methoxymethamphet-amine (HMMA). It has been applied to the analysis of plasma and urine samples from healthy recreational users of MDMA who participated voluntarily in a clinical trial and received 100 mg (R,S)-MDMA. HCl orally. (R)/(S) ratios both in plasma (0-48 h) and urine (0-72 h) for MDMA and MDA were >1 and <1, respectively. Ratios corresponding to HHMA and HMMA, close to unity, deviate from theoretical expectations and are most likely explained by the ability of MDMA to autoinhibit its own metabolism. The short elimination half-life of (S)-MDMA (4.8 h) is consistent with the subjective effects and psychomotor performance reported in subjects exposed to MDMA, whereas the much longer half-life of the (R)-enantiomer (14.8 h) correlates with mood and cognitive effects experienced on the next days after MDMA use.

regards,

methyl_ethyl

[Rhodium]

Chromatographic Methods for the Identification of the New Hallucinogen, 4-Methyl-2,5-dimethoxy-?-methylphenethylamine, and Related Drugs
K. Genest and D. W. Hughes

The Analyst, Vol. 93, No 1109 485-489 (1968)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/dom.chromatography.pdf)

Summary
Thin-layer and gas-chromatographic methods are described for the detection of  4-methyl-2,5-dimethoxy-?-methylphenethylamine in the sub-microgram range. Chromatographic criteria of identity for this new hallucinogen and for the related amines, amphetamine, methamphetamine, mescaline, and the hallucinogens, dimethyltryptamine and bufotenine are also reported.
____ ___ __ _

Crystal and Molecular Structure of the Psychotropic Drug 2-(4-Ethyl-2,5-dimethoxyphenyl)-1-methylethylamine (4-Ethyl-2,5-dimethoxyamphetamine)
Olga Kennard, Carmel Giacovazzo, Alan S. Horn, Romano Mongiorgi and Lodovico Riva di Sanseverino

J. Chem. Soc. Perkin Trans. 2, 1160-1163 (1974)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/doet.crystal.structure.pdf)

Summary
The molecular conformation of the title compound was determined by X-ray diffraction analysis. The crystals are triclinic. a = 7.43(4). b = 16.73(4). c = 5.25(6) Å. ? = 93° 30'. ? = 87° 30'. ? = 96° 18', P1, Z = 2. The structure was solved by direct methods. The molecular conformation resembles that of 2,4,5-trimethoxyamphetamine and differs from other substituted phenethylamines including dopamine hydrochloride and norepinephrine hydrochloride. This is the first determination of a free base in this class of compounds.
____ ___ __ _

Forensic Aspects of High-Pressure Liquid Chromatography
B. B. Wheals

Journal of Chromatography, 122, 85–105 (1976)

(https://www.thevespiary.org/rhodium/Rhodium/djvu/hplc.forensic.aspects.djvu)

Summary
This paper reviews the applications of high-pressure liquid chromatography (HPLC) to forensic problems, and discusses some of the developments that have taken place in the use of the technique in the Metropolitan Police Laboratory. Preparation of octadecyltrichlorosilane-modified silica is described and some of the chromatographic characteristics of this material are investigated. Applications of HPLC to the analysis of cannabis, opium alkaloids, amphetamine-related materials, LSD and polynuclear hydrocarbons are described.
____ ___ __ _

The separation of a wide range of drugs of abuse by high-pressure liquid chromatography
I. Jane

Journal of Chromatography, 111, 227-233 (1975)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/hplc.drugs-of-abuse.separation.pdf)

[Rhodium]

Impurity profiling of seized MDMA tablets by capillary gas chromatography
Fabien Palhol, Sophie Boyer, Norbert Naulet, Martine Chabrillat

Anal. Bioanal. Chem. 374(2), 274-281 (2002)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/forensic/mdma.tablets.impurity.profiling.pdf)

Abstract
Impurity profiles of 3,4-methylenedioxymethylamphetamine (MDMA) tablets seized in France have been examined. The samples were extracted with methylene chloride under basic conditions and then analyzed by capillary gas chromatography. Almost 30 compounds were identified as precursors, intermediates and by-products. Palmitic and stearic acid were also found as tableting materials. The comparison of the different profiles obtained by the reported procedure provided very useful information about the synthetic processes used by clandestine laboratories and enabled a classification into several groups of profiles. According to these results, the reductive amination route appears to be the most common synthetic pathway in Western Europe. Furthermore, 3,4-methylenedioxyphenyl-2-propanone seems to be the most used precursor in clandestine laboratories.


Fig. 5 Structure of impurities found in MDMA tablets.

[Lenin]

Thanks for the various forensic related articles Rhodium!

Comrade Lenin has been reading some of them and has a question concerning the following article: Fabian M. Dayrit and Morphy C. Dumlao; Impurity profiling of methamphetamine hydrochloride drugs seized in the Philippines (

https://www.thevespiary.org/rhodium/Rhodium/pdf/forensic/meth.hcl.impurities.philippines.pdf

)

The abstract reads: 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.

Is there anyone who can follow their hypothesis for the formation of p-bromotoluene? The route they suggest makes Lenin raise his eyebrows...

[Lilienthal]

Compound 18 looks very interesting, unfortunately they don't comment on it.

[Chimitant]

Seems they investigated MDNA tablets contaminated with amphetamine and cocaine. Phtalates seem strange to me in a MDMA tablet, may be from plastic bags they have been stored in ?  What about compound 22? Is that used as a cutting agent?

[pashov]

Hmm.. How does number 7 in "Impurity profiling of seized MDMA tablets by capillary gas chromatography" happen?

[moo]

Probably by reductive amination of piperonal (no. 5) with methylamine.

[methyl_ethyl]

Capillary Electrophoresis Analysis of a Wide Variety
of Seized Drugs
Ira S. Lurie Patrick A. Hays Kimberly Parker
Electrophoresis 2004, 25, 1580–1591
DOI:

10.1002/elps.200405894

Capillary electrophoresis methodology is presented for the routine analysis of a wide variety of seized drugs using the same capillary with dynamic coatings and multiple run buffers. The types of exhibits analyzed using diode array UV detection include phenethylamines, cocaine, oxycodone, heroin, lysergic acid diethylamide (LSD), opium, hallucinogenic mushrooms, and G-Hydroxybutyrate G-butryolactone (GHB-GBL} Both qualitative and quantitative analyses are achieved using run buffers that contain additives that provide for secondary equilibrium and/or dynamic coating of the capillary. Dynamic coating of the capillary surface is accomplished by rapid flushes of 0.1 N sodium hydroxide, water, buffer containing polycation coating reagent, and a buffer containing a polyanionic coating reagent (with or without cyclodextrin(s)) or a micelle coating reagent. Dynamic coating with a polyanionic coating reagent is used for the analysis of moderately basic seized drugs and adulterants. The use of cyclodextrin in the run buffer not only allows for chiral analysis but also greatly enhances separation selectivity for achiral solutes. A capillary dynamically coated with a micelle allows for the analysis of neutral, acidic, and weakly basic drugs (GHB, GBL and neutral, acidic, and weakly basic adulterants). Dynamic coating, which gives rise to a relatively high and robust electroosmotic flow at pH, 7, allows for rapid, precise and reproducible separations. For a wide variety of drugs, excellent linearity and migration time precision and good peak area precision (external and internal standard) is obtained. Quantitative results for synthetic mixtures are in good agreement with actual values. Screening for adulterants is greatly enhanced by the use of automated library searches.

regards,

methyl_ethyl

[Rhodium]

Analyses of impurities in methamphetamine by inductively coupled plasma mass spectrometry and ion chromatography
Shin-Ichi Suzuki, Hitoshi Tsuchihashi. Kunio Nakajima, Akira Matsushita, Takeo Nagao

J. Chrom. 437, 322-327 (1988)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/meth.impurity.analysis.icp-ms.pdf)
____ ___ __ _

Use of Bonded-Phase Silica Sorbents for Rapid Sampling of Impurities in Illicit Amphetamine for High-Performance Liquid Chromatographic Analyses
Marit Lambrechts and Knut E. Rasmussen

J. Chrom. 331, 339-348 (1985)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/amph.impurity.sampling.pdf)

Summary
A simple and rapid method has been developed for the extraction of impurities from illicit amphetamine samples using bonded-phase silica sorbents. The drug is dissolved in phosphate buffer (pH 7) and added to a C₈ Bond Elut™ extraction column. The column is washed with water, and the impurities are then eluted with acetonitrile. The eluate is directly injected into the liquid chromatograph. This sample preparation technique has been compared with the traditional liquid–liquid extraction method. High-performance liquid chromatographic analysis of the impurities is carried out on a reversed-phase C₁₈ column with an acetonitrile–water gradient as mobile phase. Peaks are monitored by UV detection at 220 and 254 nm. A series of seized amphetamine samples has been analysed, and the procedure gives detailed impurity patterns suitable for the comparison of samples. Compounds are identified by absorbance ratios (A₂₂₀/A₂₅₄).

[Natrix]

Identificazione della 4-bromo-2,5-dimetossiamfetamina (DOB) in compresse clandestine sequestrate in Italia
FURNARI, OTTAVIANO, ROSATI

Ann. Ist. Super. Sanità, vol. 37, n. 2 (2001), pp. 297-300

(http://www.iss.it/publ/anna/2001/2/372297.pdf)

Summary
(Identification of the 4-bromo-2,5-dimetoxyamphetamine (DOB) encountered in illicit tablets seized in Italy)
Some of the molecules belonging to the amphetamines group (4-bromo-2,5-dimethoxyamphetamine, DOB) or to the phenethylamines (4-bromo-2,5-dimethoxy-phenethylamine, 2C-B or Nexus) have closely related structures that make their identification quite difficult. The unambiguous identification is crucial in forensic responses. This paper describes the analytical approach used to achieve the identification of the main ingredient contained in tablets seized in the illicit market of Rome (Italy) and submitted to our laboratory by the Court of Law of Rome. The procedure entails the basic extraction of the main ingredient from the tablets with tert-butyl methyl ether followed by qualitative gas chromatographic mass-spectrometric (GC-MS) analysis using both electron impact detection (EI) and chemical ionization (CI). The examination of the mass spectra obtained from the native molecule and from its pentafluoropropionyl-derivative allows the structural identification of the side chain and the substitutions on the aromatic ring. This analytical approach can thus be useful to distinguish between amphetamine-like and phenetylamine-like compounds using instruments and techniques commonly available in the forensic toxicology laboratories.

[methyl_ethyl]

I swore I posted this previously however it is not coming up in the search engine.

Determination of MDMA, MDEA and MDA in urine by high
performance liquid chromatography with fluorescence detection
Jos Luiz da Costa, Alice Aparecida da Matta Chasin
Journal of Chromatography B, 811 (2004) 41–45
DOI:

10.1016/j.chromb.2004.03.076

Abstract:
This paper describes the development and validation of analytical methodology for the determination of the use of MDMA, MDEA and
MDA in urine. After a simple liquid extraction, the analyses were carried out on a high performance liquid chromatography (HPLC) in an
octadecyl column, with fluorescence detection. The mobile phase using a sodium dodecyl sulfate ion-pairing reagent allows good separation
and efficiency. The method showed good linearity and precision. Recovery was between 85 and 102% and detection limits were 10, 15 and
20 ng/ml for MDA, MDMA and MDEA, respectively. No interfering substances were detected with fluorescence detection.


Question for all y'all chromatographic professionals.

I notice that the y axis in the chromatograms in the above pdf. is measured in %f.  I have found this is the norm when dealing with hp 1049 detectors usually running chemstation software.  I am not a fan of chemstation software, nor do I favor Agilent/HP Liquid Chromatographs.  I have found that Waters LC's running Empower/Milennium and using a Waters 474 fluorescence detector measure mV along the Y axis, which makes sense to me.  I was wondering if anyone actually knows what %f is.  I would assume that it could not simply be % of total fluorescence (because it does not add up that way).  My problem lies in transferring a method from an Agilent platform running chemstation to a Waters platform running Empower Software.  Perhaps the actual difference lies in how the detectors actually measure the fluorescence.  If this is the case I doubt there would be an accurate means of comparing the two detectors/Platforms.

Any thoughts/comments on the topic would be greatly appreciated.

much_love

methyl_ethyl