Bank security dye packs: synthesis, isolation, and characterization of chlorinated products of bleached 1-(methylamino)anthraquinone

Banknote evidence is often submitted after a suspect has attempted to disguise or remove red dye stain that has been released because of an anti-theft device that activates after banknotes have been unlawfully removed from bank premises. Three chlorinated compounds have been synthesized as forensic chemical standards to indicate bank security dye bleaching as a suspect's intentional method for masking a robbery involving dye pack release on banknotes. A novel, facile synthetic method to provide three chlorinated derivatives of 1-(methylamino)anthraquinone (MAAQ) is presented. The synthetic route involved Ultra Clorox bleach as the chlorine source, iron chloride as the catalyst, and MAAQ as the starting material and resulted in a three-component product mixture. Two mono-chlorinated isomers (2-chloro-1-(methylamino)anthraquinone and 4-chloro-1-(methylamino)anthraquinone) and one di-chlorinated compound (2,4-dichloro-1-(methylamino)anthraquinone) of the MAAQ parent molecule were detected by gas chromatography mass spectrometry (GC-MS), and subsequently isolated by liquid chromatography (LC) with postcolumn fraction collection. Although GC-MS is sensitive enough to detect all of the chlorinated products, it is not definitive enough to identify the structural isomers. Liquid-state nuclear magnetic resonance (NMR) spectroscopy was utilized to elucidate structurally the ortho- and para-mono-chlorinated isomers once enough material was properly isolated. A reaction mechanism involving iron is proposed to explain the presence of chlorinated MAAQ species on stolen banknotes after attempted bleaching.     

Differentiation of side chain isomers of ring-substituted amphetamines using gas chromatography/infrared/mass spectrometry (GC/IR/MS).

Common analytical methods used for identifying samples obtained from clandestine laboratories were evaluated for their ability to differentiate between possible amphetamine isomers and homologs. A series of ring-substituted (4-methyl, 4-methoxy, and 3,4-methylenedioxy) amphetamine and N-methylphenethylamine isomers was analyzed using color tests, thin-layer chromatography, gas chromatography/mass spectrometry (GC/MS) and GC/infrared (GC/IR). The N-acetyl derivatives of the isomers were analyzed using GC/IR/MS. GC/IR/MS readily differentiated the 4-methylphenylalkylamine isomers. MS and IR spectra were also obtained for each pair of the 4-methoxyphenylalkylamine isomers and the 3,4-methylenedioxyphenylalkylamine isomers, but differentiation via GC/IR/MS was difficult. The N-acetyl derivatives of each pair of isomers could be readily differentiated using GC/IR/MS. Good library researchable spectra for N-acetylamphetamine could be obtained for IR identification with 10 ng (on-column) and MS identification with 2 ng. The spectrometrically independent IR and MS data obtained for the N-acetyl derivatives indicated that the combination of GC/IR/MS can add a significant level of confidence in the analysis of ring-substituted arylalkylamines.     

The Psilocin (4-hydroxy-N,N-dimethyltryptamine) and Bufotenine (5-hydroxy-N,N-dimethyltryptamine) Case: Ensuring the Correct Isomer has Been Identified

Psilocin (4-hydroxy-N,N-dimethyltryptamine, 4-HO-DMT) and bufotenine (5-hydroxy-N,N-dimethyltryptamine, 5-HO-DMT), which are both naturally occurring compounds, are classified as controlled substances in numerous countries due to their pharmacological activities and recreational usage. There are two other benzene ring regioisomers, 6-hydroxy-N,N-dimethyltryptamine (6-HO-DMT) and 7-hydroxy-N,N-dimethyltryptamine (7-HO-DMT), which are not classified by name as controlled substances, and which were synthesized for this current work. The four isomers were analyzed using routine methodologies employed by the Israel's Police Division of Identification and Forensic Science (DIFS) Laboratory, namely thin layer chromatography (TLC), Fourier transform infrared spectroscopy (FTIR), and gas chromatography mass spectroscopy (GC-MS). It was found possible to differentiate the four isomers. Forensic specimens that were suspected to be psilocybe mushrooms were examined, confirming that it is now possible to unequivocally identify the presence of psilocin and rule out the presence of its other isomers.     

The analysis of substituted cathinones. Part 2: an investigation into the phenylacetone based isomers of 4-methylmethcathinone and N-ethylcathinone

During the analysis of "seized samples", suspected of containing 4-methylmethcathinone (mephedrone) and N-ethylcathinone (ethcathinone) additional compounds were observed in the GCMS chromatogram. These compounds were suspected to be the corresponding phenylacetone isomers of mephedrone and ethcathinone respectively. These isomers are referred to as iso-mephedrone and iso-ethcathinone, respectively. The identity of these compounds was verified by synthesising the isomers from known starting materials and comparing them with the compounds found in the seized samples. Analytical data, GCMS, NMR and IR on these compounds are provided. Possible explanations for the presence of these compounds in the seized samples are explored. Contaminated starting material is one suggestion. Rearrangement of the propiophenone based product to the phenylacetone based product is also suggested. The reaction of the α-bromopropiophenone with a primary amine can also lead to the phenylacetone based product. The presence of these isomeric compounds in seized samples could be used to compare different samples and attempt to establish a common origin.     

Schedules of controlled substances: placement of ezogabine into Schedule V. Final rule

With the issuance of this final rule, the Administrator of the Drug Enforcement Administration (DEA) places the substance ezogabine, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible, into Schedule V of the Controlled Substances Act (CSA). This action is pursuant to the CSA which requires that such actions be made on the record after opportunity for a hearing through formal rulemaking.     

Mass spectrometry as an aid in the detection and identification of piperidyl benzilates and related glycolates.

On the basis of the data presented above the following conclusions may be drawn. 1. The molecular ion peaks of most of the compounds examined are relatively weak but usually easily discernible to permit molecular weight determination. 2. The mass spectra of benzilate esters exhibit a relatively intense peak at m/e 183, and monitoring of this ion can serve as a means for preliminary screening for the presence of this type of a system. 3. Related esters exhibit a similar type of fragmentation resulting in a fragment ion analogous to m/e 183 but shifted by the appropriate number of mass units according to the substituents present. 4. Cleavage of the piperidine ring-ester oxygen bond in 3 and 4-substituted isomers is followed by selective losses of hydrogen radicals to produce ions of type e, f, and g as indicated above. It is significant that in a related piperidine ring system (methylphenidate) substituted in the 2 position, the same type of cleavage results in no further hydrogen losses [16] because of charge stabilization from the ring nitrogen (ion j, Fig. 17) [17]. In other words, the tendency to form a conjugated ion following initial bond cleavage can serve as a means for identifying the position of substitution on the ring and for distinguishing positional isomers.     

Characterization and differentiation of cyclopropylfentanyl from E-crotonylfentanyl, Z-crotonylfentanyl,and 3-butenylfentanyl

Recently, a sample containing cyclopropylfentanyl was analyzed at this laboratory. Cyclopropylfentanyl began to appear in the United States' illicit drug markets in 2017. Unfortunately, cyclopropylfentanyl presents an analytical challenge due to its mass spectrum being almost identical to that of crotonylfentanyl. There are two possible isomers of crotonylfentanyl, Z- and E- crotonylfentanyl. In order to provide sufficient analytical data to distinguish the two isomers of crotonylfentanyl and cyclopropylfentanyl, crotonylfentanyl was synthesized and fully characterized. Each isomer was analyzed via nuclear magnetic resonance spectroscopy, gas chromatography–mass spectrometry, and Fourier transform infrared spectroscopy. During the synthesis of crotonylfentanyl, an unknown compound was formed. The identification of this compound and the analytical characterization of the two isomers of crotonylfentanyl are presented. Through the comparison of these compounds, it was confirmed that cyclopropylfentanyl can be differentiated from crotonylfentanyl.     

Schedules of controlled substances: placement of 5-methoxy-N,N-dimethyltryptamine into Schedule I of the Controlled Substances Act. Final rule

With the issuance of this final rule, the Deputy Administrator of the Drug Enforcement Administration (DEA) places the substance 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), including its salts, isomers and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible, into schedule I of the Controlled Substances Act (CSA). This action by the DEA Deputy Administrator is based on a scheduling recommendation from the Assistant Secretary for Health of the Department of Health and Human Services (DHHS) and a DEA review indicating that 5-MeO-DMT meets the criteria for placement in schedule I of the CSA. This final rule will impose the criminal sanctions and regulatory controls of schedule I substances under the CSA on the manufacture, distribution, dispensing, importation, exportation, and possession of 5-MeO-DMT.     

Forensic toxicologic analysis of methamphetamine and amphetamine optical isomers by high performance liquid chromatography

Optical isomers (d and l) and racemic compounds (dl) of methamphetamine (MAMP) and amphetamine (AMP), and biologic materials including those substances, could be analyzed by high performance liquid chromatography. Examining the temperature for the analysis, 40 degrees C was the optimal condition in the reproducibility of separated MAMP-isomers. The reproducibility at the temperature did not vary significantly. The measured values of optical isomers were 0.116 +/- 0.012, 1.082 +/- 0.070 and 8.984 +/- 0.136 for the mixing ratios (l/d) of 0.111, 1.000, and 9.000, respectively. The detection limit for both d- and l-isomers was 25 ng. The analytic result of hair specimens from two stimulant abusers by the present method indicates that they contained only d-MAMP and d-AMP, which is believed to have the strongest pharmacologic effect among the optical isomers of MAMP. The coefficient of variation in the analysis of five replicate standards, prepared by adding 1,000 ng each of racemate MAMP and AMP to hair, was less than 4%. The measured value against l/d = 1.000 was 1.040 +/- 0.040 in MAMP and 0.980 +/- 0.030 in AMP. The detection limit for both racemate MAMP and AMP accumulated in hair was 250 ng. The analysis of the optical isomers by our method would contribute to identifying the smuggling routes or the illicit method.     

Schedules of controlled substances: temporary placement of three synthetic cathinones in Schedule I. Final Order

The Administrator of the Drug Enforcement Administration (DEA) is issuing this final order to temporarily schedule three synthetic cathinones under the Controlled Substances Act (CSA) pursuant to the temporary scheduling provisions of 21 U.S.C. 811(h). The substances are 4-methyl-N-methylcathinone (mephedrone), 3,4-methylenedioxy-N-methylcathinone (methylone), and 3,4-methylenedioxypyrovalerone (MDPV). This action is based on a finding by the Administrator that the placement of these synthetic cathinones and their salts, isomers, and salts of isomers into Schedule I of the CSA is necessary to avoid an imminent hazard to the public safety. As a result of this order, the full effect of the CSA and its implementing regulations including criminal, civil and administrative penalties, sanctions and regulatory controls of Schedule I substances will be imposed on the manufacture, distribution, possession, importation, and exportation of these synthetic cathinones.     

Schedules of controlled substances: placement of Zopiclone into schedule IV. Final rule

With the issuance of this final rule, the Deputy Administrator of the Drug Enforcement Administration (DEA) places the substance, zopiclone, including its salts, isomers and salts of isomers into Schedule IV of the Controlled Substances Act (CSA). As a result of this rule, the regulatory controls and criminal sanctions of Schedule IV will be applicable to the manufacture, distribution, dispensing, importation and exportation of zopiclone and products containing zopiclone.     

Definition of "positional isomer" as it pertains to the control of schedule I controlled substances. Final rule

On May 25, 2006, DEA published a Notice of Proposed Rulemaking which proposed the addition of a specific definition for the term "positional isomer" to allow for the systematic determination of which isomers of schedule I substances would be considered to be "positional," and therefore, subject to schedule I control. This rulemaking finalizes that definition. The Controlled Substances Act (CSA) and its implementing regulations specify which hallucinogenic substances are considered schedule I controlled substances. The CSA states that all salts, isomers, and salts of isomers of these substances are also schedule I controlled substances. In non-technical terms, an isomer of a substance is a different compound, but a compound which has the same number and kind of atoms. The terms "optical isomer" and "geometric isomer" are specific scientific terms and it is easy to determine whether one substance is an optical or geometric isomer of another. The term "positional isomer," however, is subject to scientific interpretation. The addition of a definition for the term "positional isomer" will assist legitimate research[ers] and industry in determining the control status of materials that are "positional isomers" of schedule I hallucinogens. While the DEA will remain the authority for ultimately determining the control status of a given material, providing a specific definition for "positional isomer" will ensure consistent criteria are utilized in making these determinations. This rule does not change existing laws, regulations, policies, processes, and procedures regarding the determination of control status for schedule I hallucinogenic substances. This rule merely makes available to the public the longstanding definition of "positional isomer" which DEA has used when making these scheduling determinations. This rule is relevant only to specialized forensic or research chemists. Most of these individuals are existing DEA registrants who are authorized by the DEA to handle schedule I hallucinogenic substances.     

Schedules of controlled substances: placement of lisdexamfetamine into schedule II. Final rule

With the issuance of this final rule, the Deputy Administrator of the Drug Enforcement Administration (DEA) places the substance lisdexamfetamine, including its salts, isomers and salts of isomers into schedule II of the Controlled Substances Act (CSA). As a result of this rule, the regulatory controls and criminal sanctions of schedule II will be applicable to the manufacture, distribution, dispensing, importation and exportation of lisdexamfetamine and products containing lisdexamfetamine.     

Potassium nitrite reaction with 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in urine in relation to the drug screening analysis.

Recently potassium nitrite has been used as an adulterant to interfere with the analysis of 11-nor-delta 9-tetrahydro-cannabinol-9-carboxylic acid (THC-COOH) in urine. A comprehensive study of the THC-COOH and nitrite reaction chemistry and stability under various conditions is presented. Reverse phase high performance liquid chromatography (HPLC) and negative electrospray mass spectrometry (ESMS) results are given to substantiate the derived reaction mechanism and properties leading to reaction termination. The addition of potassium carbonate as a buffering agent prior to or following sample void as a means of preventing the formation of a nitroso-complexed form of the 11-nor-delta 9+-tetrahydrocannabinol-9-carboxylic acid is evaluated.     

Characterization and Differentiation of Geometric Isomers of 3‐methylfentanyl Analogs by Gas Chromatography/Mass Spectrometry,Liquid Chromatography/Mass Spectrometry,and Nuclear Magnetic Resonance Spectroscopy

The cis and trans isomers of 3‐methylfentanyl and its three analogs were chemically synthesized, and these compounds were characterized and differentiated by gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS), and nuclear magnetic resonance (NMR) spectroscopy. The cis and trans isomers of the 3‐methylfentanyl analogs were completely separated by GC/MS. Although the high temperature of the GC injection port caused thermal degradation of β‐hydroxy‐3‐methylfentanyl, the degradation was completely suppressed by trimethylsilyl derivatization. The isomers were also well separated by LC/MS on an octadecylsilyl column with 10 mM ammonium acetate and methanol as the mobile phase. The proton NMR signals were split when the hydrochloride salts of the 3‐methylfentanyl analogs were dissolved in deuterated chloroform because stereoisomers were formed by the coordination of the hydrochloride proton to the nitrogen of the piperidine ring of the 3‐methylfentanyl analogs.     

Wisdom or Indifference? The Principles of Representative Government in the Eyes of the French Voters

This contribution attempts to assess qualitatively the current views of ordinary French citizens about political representation in general and their MPs in particular. In contrast to the Tocquevillian idea of an unequivocal egalitarian claim rising from the people, the results of the present study support the view that citizens tend to adopt both democratic and aristocratic principles in their perceptions of political representation. General support for the electoral procedure captures such ambiguity as elections are not only legitimate on democratic grounds (the egalitarian civic participation) but also on aristocratic grounds (the selection of the best). This study follows an original method involving analysis of discussions from 11 focus groups within French constituencies in 2010–11. The results of an experimental design comparing various kinds of elected position (parents' representatives, workers' representatives, MPs and the President of the Republic) are presented and discussed.     

Identifying reliable ions for the statistical differentiation of structurally similar fentanyl analogs

Definitive identification of fentanyl analogs based on mass spectral comparison is challenging given the high degree of structural and, hence, spectral similarity. To address this, a statistical method was previously developed in which two electron-ionization (EI) mass spectra are compared using the unequal variance t-test. Normalized intensities of corresponding ions are compared, testing the null hypothesis (H₀) that the difference in intensity is equal to zero. If H₀ is accepted at all m/z values, the two spectra are statistically equivalent at the specified confidence level. If H₀ is not accepted at any m/z value, then there is a significant difference in intensity at that m/z value between the two spectra. In this work, the statistical comparison method is applied to distinguish EI spectra of valeryl fentanyl, isovaleryl fentanyl, and pivaloyl fentanyl. Spectra of the three analogs were collected over a 9-month period and at different concentrations. At the 99.9% confidence level, the spectra of corresponding isomers were statistically associated. Spectra of different isomers were statistically distinct, and ions responsible for discrimination were identified in each comparison. To account for inherent instrument variations, discriminating ions for each pairwise comparison were ranked based on the magnitude of the calculated t-statistic (t_calc) value. For a given comparison, ions with higher t_calc values are those with the greatest difference in intensity between the two spectra and, therefore, are considered more reliable for discrimination. Using these methods, objective discrimination among the spectra was achieved and ions considered most reliable for discrimination of these isomers were identified.     

The analysis of substituted cathinones. Part 3. Synthesis and characterisation of 2,3-methylenedioxy substituted cathinones

The first synthesis of the 2,3-isomers of MDPV, butylone and methylone is reported. The isomers were characterised by (1)H and (13)C NMR spectroscopy and compared to the corresponding 3,4-isomers. A GC method is described which separates the 3,4- and the 2,3-isomers from each other. IR spectra of the 2,3-isomers are also compared with the corresponding 3,4-isomers. Two seized drug samples were analysed by GCMS and the samples were found to contain the 3,4-isomers.     

Validated method for the simultaneous determination of Delta9-THC and Delta9-THC-COOH in oral fluid, urine and whole blood using solid-phase extraction and liquid chromatography-mass spectrometry with electrospray ionization

A fully validated, sensitive and specific method for the extraction and quantification of Delta(9)-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-Delta(9)-THC (THC-COOH) and for the detection of 11-hydroxy-Delta(9)-THC (11-OH THC) in oral fluid, urine and whole blood is presented. Solid-phase extraction and liquid chromatography-mass spectrometry (LC-MS) technique were used, with electrospray ionization. Three ions were monitored for THC and THC-COOH and two for 11-OH THC. The compounds were quantified by selected ion recording of m/z 315.31, 329.18 and 343.16 for THC, 11-OH THC and THC-COOH, respectively, and m/z 318.27 and 346.26 for the deuterated internal standards, THC-d(3) and THC-COOH-d(3), respectively. The method proved to be precise for THC and THC-COOH both in terms of intra-day and inter-day analysis, with intra-day coefficients of variation (CV) less than 6.3, 6.6 and 6.5% for THC in saliva, urine and blood, respectively, and 6.8 and 7.7% for THC-COOH in urine and blood, respectively. Day-to-day CVs were less than 3.5, 4.9 and 11.3% for THC in saliva, urine and blood, respectively, and 6.2 and 6.4% for THC-COOH in urine and blood, respectively. Limits of detection (LOD) were 2 ng/mL for THC in oral fluid and 0.5 ng/mL for THC and THC-COOH and 20 ng/mL for 11-OH THC, in urine and blood. Calibration curves showed a linear relationship for THC and THC-COOH in all samples (r(2)>0.999) within the range investigated. The procedure presented here has high specificity, selectivity and sensitivity. It can be regarded as an alternative method to GC-MS for the confirmation of positive immunoassay test results, and can be used as a suitable analytical tool for the quantification of THC and THC-COOH in oral fluid, urine and/or blood samples.     

The analysis of substituted cathinones. Part 1: chemical analysis of 2-, 3- and 4-methylmethcathinone

The ring substituted methyl isomers of methcathinone, 2-, 3- and 4-methylmethcathinone were analysed. The 2- and 3-isomers were synthesized. The 4-methylmethcathinone isomer is also known as mephedrone and has been widely studied. We present GCMS, NMR and IR data for the three isomers. We show that the three isomers can be separated by GCMS and that the IR spectra for the three compounds can be used to distinguish between them. A seized sample was analysed and it was found to contain 4-methylmethcathinone and benzocaine.