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.

Changes in illicit cocaine hydrochloride processing identified and revealed through multivariate analysis of cocaine signature data.

For nearly 30years, the methods utilized in illicit cocaine hydrochloride production have remained relatively consistent. Cocaine hydrochloride is typically produced one kilogram at a time. As a result, each individual kilogram is unique and distinct from other kilograms in any particular seizure based on the total alkaloid profile, occluded solvent profile, and isotopic signature. Additionally, multi-kilogram cocaine seizures are often comprised of cocaine from several different coca growing regions. There has been a documented shift in this type of processing based on the recent analysis of a large cocaine seizure in the Eastern Pacific. Signature analyses of samples from 21kg randomly selected from a 517kg seizure were virtually identical. Triplicate analyses of each sample via gas chromatography with flame ionization detection, static headspace gas chromatography mass spectrometry, and isotope ratio mass spectrometry were completed. An initial outlier evaluation of the data and an in-depth univariate analysis indicated there was no statistically significant difference among the 21 samples at the 95% confidence interval. Principal components analysis did reveal consistent minor deviations between the samples and known authentic data from the Nariño coca growing region of Colombia. These deviations were only observed on the latter principal components and could be explained by differences in solvent selection during cocaine hydrochloride processing. Chemical analyses in addition to a thorough statistical evaluation suggest a shift in the traditional small-batch method of cocaine processing to a multi-kilogram, high throughput approach.

The isotopic fractionation of carbon, nitrogen, hydrogen, and oxygen during illicit production of cocaine base in South America.

Stable isotope measurements have become a key component in sourcing the origin of illicit cocaine seized within the United States. Therefore, it is imperative to understand the process by which isotopes may be fractionated during illicit cocaine processing. In a controlled observational study, there was apparent isotopic fractionation of carbon, nitrogen, hydrogen, and oxygen. To investigate the potential source of the fractionation, cocaine base was fractionally precipitated from a dilute sulfuric acid solution with dilute ammonium hydroxide. The values of δ13C, δ15N, δ2H, and δ18O for each fraction were measured by isotope ratio mass spectrometry (IRMS). There was an equilibrium fractionation observed in all measured stable isotopes. Early fractions were depleted, and later fractions were enriched, with 15N and 2H being the most affected. The described trend is opposite of the Rayleigh distillation observed for cocaine hydrochloride precipitation.

Geographically Sourcing Cocaine's Origin - Delineation of the Nineteen Major Coca Growing Regions in South America.

Previously, geo-sourcing to five major coca growing regions within South America was accomplished. However, the expansion of coca cultivation throughout South America made sub-regional origin determinations increasingly difficult. The former methodology was recently enhanced with additional stable isotope analyses ((2)H and (18)O) to fully characterize cocaine due to the varying environmental conditions in which the coca was grown. An improved data analysis method was implemented with the combination of machine learning and multivariate statistical analysis methods to provide further partitioning between growing regions. Here, we show how the combination of trace cocaine alkaloids, stable isotopes, and multivariate statistical analyses can be used to classify illicit cocaine as originating from one of 19 growing regions within South America. The data obtained through this approach can be used to describe current coca cultivation and production trends, highlight trafficking routes, as well as identify new coca growing regions.

Headspace-gas chromatographic-mass spectrometric analysis of South American commercial solvents and their use in the illicit conversion of cocaine base to cocaine hydrochloride.

This study presents data that establish the makeup of solvents utilized in illicit cocaine hydrochloride production, as determined via the identification of the occluded solvents in the crystal matrix of the final product. The occluded solvent ratios can differ dramatically from the ratios of the original processing solvents. Additionally, the presented data suggest the diversion of commercial solvents to illicit cocaine hydrochloride laboratories. Thirty-five commercial solvents were obtained from five chemical manufacturing companies in South America. Each solvent was qualitatively and quantitatively analyzed using static headspace-gas chromatography-mass spectrometry (HS-GC-MS). After obtaining the chemical profile for each commercial solvent, solvents and/or solvent mixtures were prepared to be comparable in composition to several of the commercial products. Over 90 individual batches of cocaine hydrochloride were prepared from cocaine base using these solvents or solvent mixtures, which match those most commonly employed in clandestine laboratories. Additionally, a number of unique manufacturing by-products produced from processing solvents were identified, and their significance is discussed.

Rapid determination of the isomeric truxillines in illicit cocaine via capillary gas chromatography/flame ionization detection and their use and implication in the determination of cocaine origin and trafficking routes.

The isomeric truxillines are a group of minor alkaloids present in all illicit cocaine samples. The relative amount of truxillines in cocaine is indicative of the variety of coca used for cocaine processing, and thus, is useful in source determination. Previously, the determination of isomeric truxillines in cocaine was performed with a gas chromatography/electron capture detection method. However, due to the tedious sample preparation as well as the expense and maintenance required of electron capture detectors, the protocol was converted to a gas chromatography/flame-ionization detection method. Ten truxilline isomers (alpha-, beta-, delta-, epsilon-, gamma-, omega, zeta-, peri-, neo-, and epi-) were quantified relative to a structurally related internal standard, 4',4″-dimethyl-α-truxillic acid dimethyl ester. The method was shown to have a linear response from 0.001 to 1.00 mg/mL and a lower detection limit of 0.001 mg/mL. In this method, the truxillines are directly reduced with lithium aluminum hydride and then acylated with heptafluorobutyric anhydride prior to analysis. The analysis of more than 100 cocaine hydrochloride samples is presented and compared to data obtained by the previous methodology. Authentic cocaine samples obtained from the source countries of Colombia, Bolivia, and Peru were also analyzed, and comparative data on more than 23,000 samples analyzed over the past 10 years with the previous methodology is presented.

Chemosystematic identification of fifteen new cocaine-bearing Erythroxylum cultigens grown in Colombia for illicit cocaine production.

Colombian coca farmers have historically cultivated three varieties of coca for cocaine production (Erythroxylum novogranatense var. novogranatense, Erythroxylum novogranatense var. truxillense, and Erythroxylum coca var. ipadu). Within the past 13 years, 15 new cultigens of cocaine-bearing Erythroxylum have been propagated by Colombian coca farmers; each with differing physical characteristics, yet producing cocaine alkaloids at similar levels found in the historical and native varieties. Fifteen new cultigens were collected from throughout Colombia and propagated along with the three historical varieties within an experimental field in Colombia. Five plants/cultigen were randomly selected and examined for alkaloid content to determine their varietal characteristics when compared to the three known varieties. Ten cultigens gave classic Erythroxylum coca var. ipadu alkaloid profiles, four cultigens produced alkaloid profiles consistent with a hybridization of Erythroxylum novogranatense and Erythroxylum coca var. ipadu, while one cultigen gave heterogeneous alkaloid profiles that could not be characterized.