Synthetic Cannabinoid structure classification using the bridge carbonyl frequency in vapor phase

Abstract

Synthetic Cannabinoids are the most complex branch of designer drugs encountered in forensic chemistry. A screening method has been developed that can accurately identify the correct structural category of an unknown Synthetic Cannabinoid. Knowledge of this information is very important when no reference data or standards are available since certain sub-categories contain Schedule I Controlled Dangerous Substances. The Bridge portion of these molecules present a unique carbonyl band cluster within a small 200 wavenumber interval of the mid-infrared region that can only exist in vapor phase through GC/FTIR light-pipe technology or heated static vapor cell FTIR. This special relationship is not applicable to any other forms of solid phase vibrational spectroscopy (FTIR, RAMAN) including GC/FTIR solid-deposit techniques. The carbonyl frequency from the Bridge is used as the first step in the screening process which separates the entire forensically encountered class of Synthetic Cannabinoids into 35 sub-categories. Additional bands within the cluster from secondary functional groups, rotational isomerism, and fermi resonance add further refinement within these categories.

Claims

1. A method of analyzing a suspected synthetic cannabinoid sample, comprising the steps of: Capturing the sample in a vapor state using either a heated static vapor cell on a benchtop FTIR spectrometer or flow cell from a GC/FTIR system at temperatures between 250-290 degrees Celsius; Directing infrared radiation from the infrared spectrometer through the captured vapor of the sample; Recording the resultant absorption spectrum across a frequency interval from a starting frequency of 1840 wavenumbers to an ending frequency of 1640 wavenumbers; Identifying between one and three carbonyl infrared absorption bands in the recorded resultant absorption spectrum; Identifying a bridge frequency within said between one and three carbonyl infrared absorption bands in the recorded resultant absorption spectrum; Matching each of said between one and three carbonyl infrared absorption bands to the best fitting match from reference data representing all synthetic cannabinoid categories, using the bridge frequency as the first band to compare; and Identifying the suspected synthetic cannabinoid sample based on said matching.

2. The method of claim 1, further comprising the steps of: Sequentially repeating the steps of claim 1; Generating an infrared carbonyl absorption frequency wavenumber table, based on data obtained from pure synthetic cannabinoid reference materials in the vapor state, and classifying them into three types of absorptionsthe bridge frequency, carbonyl from secondary functional group, and unique rotational bands; Identifying the bridge frequency within each carbonyl band group which, if more than one band is present, is the band with the lowest frequency of the group; Sorting the tabulated data in the wavenumber table in order of increasing bridge frequency; and Linking said tabulated reference data directly to the overall molecular structure representing the synthetic cannabinoid category in terms of three basic pieces: the core ring, the bridge, and the secondary ring system or functional group.

3. A non-transitory, computer-readable medium containing instructions that, when executed by a computer, cause the method of claim 1 or claim 2 to be performed.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1. is a table linking all carbonyl absorption band frequencies in tabular format directly to the Synthetic Cannabinoid Categories in terms of three basic structural pieces recognizing that the implementation of these categories is the functional equivalent of indexed spectral matching analysis.

(2) FIG. 2. is the overlay of four infrared spectral plots of 5-fluoro AB-PINACA in the 1650 wavenumber region illustrating that vapor phase is the only infrared technique capable of resolving and identifying both carbonyl bands from this molecule.

(3) FIG. 3. is the overlay of three spectral plots of APINAC in the 1750 wavenumber region. Molecular rotation of this molecule is only possible in the vapor phase causing a Field Effect resulting in an additional carbonyl band as shown in the bottom spectrum. This does not occur in any form of solid phase vibrational spectroscopy all of which lead to only one single carbonyl absorption.

(4) FIG. 4. illustrates two full scale infrared spectral plots of SDB-005 and NM2201 in the vapor phase. Further proof of the Field Effect can be found by comparing the carbonyl absorptions of these two similarly structured compounds in the 1750 wavenumber region. The only difference is the addition of one extra Nitrogen atom in the indazole ring of SDB-005 splitting the carbonyl absorption into two bands. The unshared electron pair from the Nitrogen atom on the indole ring of NM2201 is too far away to interact vicinal to the carbonyl during bond rotation.

(5) FIG. 5. illustrates overlaid infrared spectral plots of two JWHO81 positional isomers comparing crystalline solid phase in contrast to vapor phase. Vapor phase (bottom) significantly enhances the single carbonyl absorption for both isomers and shifts the band away from the Wilson 8a and 8b ring stretching bands.

(6) FIG. 6. is a molecular structural diagram explaining the rules and nomenclature for dividing all Synthetic Cannabinoid categories into three basic pieces. The ring systems and functional groups present in each piece are directly linked to the infrared tabular data resulting in a basis for the identification of any unknown Synthetic Cannabinoid in terms of a basic molecular structure.

DESCRIPTION OF THE INVENTION

(7) Synthetic Cannabinoids represent the largest class of forensically encountered designer drugs. The BRIDGE TABLE represented in FIG. 1 provides a quick and accurate screening technique in order to properly identify 35 sub-categories within this class of drugs without the use of any initial standards. Since certain derivatives are Schedule I controlled dangerous substances, knowledge of the correct sub-class as a first step in the screening process is very important. An infrared spectrum of the unknown compound must be acquired in vapor phase at elevated temperatures between 250 to 290 C. by either a GC/FTIR system using light-pipe technology so that the column effluent remains in a vapor state or using a heated static vapor cell on a bench top FTIR system. All bands from the unknown spectrum between 1840-1640 cm.sup.1 are matched to the correct entry within the BRIDGE TABLE. From this, the molecular structure will be given in terms of the functional group making up the Bridge and its 2 adjoining pieces, one of which will always be a ring based system (core ring) which is present in all Synthetic Cannabinoids.

(8) The BRIDGE TABLE is a result of an infrared relationship existing within the carbonyl cluster that can only be visualized in the vapor state and is capable of filtering the Synthetic Cannabinoids into 35 sub-categories. The values used in this table were based on real data. Vapor Phase Infrared Spectra of over 200 pure reference materials were acquired using standard GC/FTIR light-pipe technology at temperatures between 250 to 280 C. From this data, the Carbonyl Frequencies from these Synthetic Cannabinoids were systematically recorded and sorted according to their chemical structure. In order to classify all structures within this group into 35 separate sub-categories, the following scheme was used:

(9) Synthetic Cannabinoids were classified according to the ring systems and functional groups present by defining each example into 3 basic pieces as designated in FIG. 6. 1. CORE RING SYSTEM (NUCLEOUS with the TAIL present)Most common would be Indole and Indazole, but can also be other ring systems such as Benzimidazole, Pyrrole, and Carbazole 2. BRIDGE (A Single Functional Group) joining the Core Ring System with another Ring or Functional Group. Examples: Ketones, Esters, and Secondary Amides 3. SECONDARY RING SYSTEM such as Naphthalene, Benzene, Quinoline or another Functional Group such as an Ester or Primary Amide

(10) Not all Synthetic Cannabinoids possess a Secondary Ring System. In some classes, this ring system is replaced by a functional group. FIG. 6 illustrates both of these examples. One is a Naphthoylindole which has naphthalene Secondary Ring System with a methanone Bridge. In the case where no secondary ring system exists, the third piece is defined by the example of ADB-PINACA in FIG. 6. The dashed line in this example shows that the Bridge is defined as the complete functional group which is bonded to the core ring system (indazole) and is a secondary amide. The third piece (second functional group) begins where the dashed line separates the Bridge on the opposite side of the core ring system. In some cases it is a second functional group bonded to another ring system. No matter how complex the third piece is, its functional group moiety is always bonded to the Bridge functional group. These rules have been consistently applied to all derivatives examined and completely define all listed sub-categories in the table.

(11) Certain sub-categories contain regulated controlled dangerous substances which can either be color coded in the Bridge Table or tagged in a digital software version. The following 12 sub-categories that contain controlled substances are listed in the format of the Bridge TableBRIDGE FUNCTIONAL GROUP/CORE RING/SECONDARY RING OR FUNCTIONAL GROUP:

(12) methanone/indole/naphthalene, methanone/indole/cyclopropane, methanone/indole/benzene, ethanone/indole/benzene, ester/indole/naphthalene, ester/indole/quinoline, secondary amide/indole/ester, secondary amide/indole/primary amide, secondary amide/indazole/adamantyl, secondary amide/indazole/ester, methanone/indazole/naphthalene, and secondary amide/indazole/1-methyl-phenylethyl

(13) The BRIDGE TABLE in FIG. 1 contains the following column headings:

(14) BRIDGE CARBONYL FREQUENCYThis contains the entire Carbonyl Frequency range found for all 35 sub-categories of the Synthetic Cannabinoids. The actual range for each category never exceeded more than 4 wavenumbers. This is the pointer index and values from this column are used to compare Carbonyl value of an unknown compound as a first step.
BRIDGE FUNCTIONAL GROUPList the type of functional groups responsible for joining the core ring and secondary ring system together: Methanone, Ethanone, Secondary Amide, or Ester.
ADDITIONAL CARBONYL FREQUENCY FROM PIECEIn some cases the Secondary Ring System is replaced with a Functional Group. If this group contains a Carbonyl moiety, the frequency is listed in this column.
UNIQUE CARBONYL FREQUENCYA few special cases exist in which additional Carbonyl bands are found as a result of either the Field Effect from rotational isomerism or Fermi Resonance.
ADJOINING PIECESThis column defines the other two ring systems and/or functional groups that are bonded to each side of the Bridge. Since the two occupy the same column, each are separated by a /. When the proper match to all Carbonyl Frequencies are found, this information coupled with the Bridge Functional Group yields the complete sub-category molecular structure.

(15) Starting from the bottom of the table and going up, the Carbonyl Bridge Frequencies are listed in ascending order. By comparing frequencies of unknown Synthetic Cannabinoids directly to this table, insights are quickly gained as to the correct Synthetic Cannabinoid Class. All sub-categories are identified by matching Bridge frequencies from unknown samples with the BRIDGE CO carbonyl value. Additional Carbonyl bands from other functional groups are also listed in the table. This also includes unique carbonyl bands from rotational isomers and fermi resonance which also gives further clarification between the categories. All carbonyl absorptions are recorded from the unknown compound between 1840-1640 cm.sup.1 and noted. The carbonyl band cluster can contain one single band to a maximum of three bands. Only one category is found in the entire table that will yield three bands; these are examples that have a secondary amide Bridge bonded to a core ring of indole and a primary amide. The special bands listed in the UNIQUE CO column are always the weakest bands in the cluster. A majority of sub-categories contain only one single carbonyl band with is easily assigned as the Bridge frequency. The last possibility arises when the unknown contains two bands within the region. In this case, the carbonyl band assigned as the Bridge frequency is the band which has the lower frequency of the two.

(16) For instance, an unknown compound (JWH-018) yields a single carbonyl frequency of 1657 cm.sup.1. This frequency is matched to the first column BRIDGE CO in the table with the range 1654-1657 yielding the class: METHANONE BRIDGE, INDOLE/NAPHTHALENE which represents a Methanone Bridge bonded to a Indole core ring and a Naphthalene secondary ring system.

(17) Another unknown compound (PX-1) gives a three carbonyl bands within the cluster range. The weakest band of the three is at 1832 cm.sup.1 and is assigned as a UNIQUE CO to the table. This leaves the other two bands at 1669 cm.sup.1 and 1723 cm.sup.1 to be assigned. The 1669 cm.sup.1 band is chosen as the Bridge Frequency since it is the lower of the two values. This value is now searched in the first column of the BRIDGE TABLE and falls within the range 1668-1671. The sub-category in this matching entry is Secondary Amide Bridge bonded to an Indole Core Ring and a Primary amide. The other two bands are identified as a Primary Amide Carbonyl band at 1723 cm.sup.1, and one unique Carbonyl band from fermi resonance at 1832 cm.sup.1.

(18) A third unknown compound (AB-FUBINACA 3-fluorobenzyl isomer) is examined in vapor phase yielding two bands at 1688 cm.sup.1 and 1726 cm.sup.1. The lower frequency value of the two bands is 1688 cm.sup.1 and is chosen to be the Bridge Carbonyl. This value falls within the range of 1685-1688 cm.sup.1 listed in the Bridge Table. This entry also matches the second band as being an additional functional group within the range of 1725-1728 cm.sup.1. The sub-category listed for these values reflect that the unknown has a Secondary Amide Bridge (absorbing at 1688 cm.sup.1) bonded to and Indazole core ring and a Primary Amide (absorbing at 1726 cm.sup.1).

(19) This invention provides a quick identity to the correct sub-category and legal status of an unknown Synthetic Cannabiniod without of a full search library or standard present for comparison. Choosing the bridge frequency in vapor phase as the first step in the presence of other carbonyl absorptions is a unique technique which can gain much insight to molecular structure from so few bands. No prior/current art exists for comparison and the history of vapor phase explains why this has never happened.