Desomorphine is a semisynthetic opioid that is responsible for the psychoactive effects of a dangerous homemade injectable mixture that goes by street name
The number of new designer drugs and older ones reappearing on the drug market is increasing and becoming a major public health concern. These designer substances are being used to substitute or mimic the effects of other controlled substances, while circumventing current drug policy and legality. Desomorphine (C17H21NO2, dihydrodesoxymorphine) is the case of a reappearance of an older designer drug as an economical substitute for heroin, first observed in the Russian Federation and Ukraine in 2003 [
“Krokodil” poses a serious threat to users due to the severe symptoms and side effects but is also a concern with regard to its potential spread to other countries. It is believed that the use of “Krokodil” has already migrated to nearby countries including Poland, Czech Republic, France, Belgium, Sweden, Norway, and other European countries due to Russian immigration [
Ambient ionization mass spectrometric techniques such as desorption electrospray ionization mass spectrometry (DESI-MS) [
Herein, we employ DESI and PSI in combination with a portable MS system for the analysis of desomorphine and its precursor codeine to show applicability to this important emerging drug. Screening of trace residues of desomorphine and codeine was conducted from surfaces commonly used or found in the storage, transport, and clandestine synthesis, reporting representative limits of detection. This work serves to show the utility of such an application to provide data of probative evidentiary value from a variety of forensic scenarios, ranging from reaction precursors, clandestine laboratory installations, seized bulk drugs, and trace evidence.
Solutions of desomorphine and codeine were obtained as 1.0 mg/mL analytical standards from Cerilliant Corp. (Round Rock, TX, USA) and serially diluted in methanol to desired concentrations of 0.10, 0.010, 0.0010, and 0.00010 mg/mL. Solutions were then spotted in predetermined amounts via adjustable micropipette onto porous Teflon well slides (Prosolia Inc., Indianapolis, IN, USA) for DESI analysis or Whatman chromatography paper (Fisher Scientific, Inc., Hampton, NH, USA) for PSI analysis according to the relationship that 1
For limits of detection studies, known masses of desomorphine or codeine were deposited onto surfaces of interest by spotting 1
Sampling of desomorphine and codeine residues from clandestine relevant surfaces with DESI-MS was performed by swabbing a ~9 cm2 area of the surface of interest near the location of analyte deposition. Swabs utilized consisted of polyurethane foam (Berkshire Corp., Great Barrington, MA, USA) moistened with a small amount spray solvent, H2O/MeOH (1 : 1, v/v) with 0.1% (v/v) formic acid, to assist in the collection of surface residues. Swabs were immediately introduced into the DESI source after collection.
For analysis with PSI-MS, Whatman chromatography paper cut into 10 mm × 5 mm isosceles triangles was employed as both the swabs and spray substrate. Prior to analysis, each triangle was saturated with methanol, similar to the protocol employed for DESI analysis, and used to swab the surface of interest. After swabbing, the paper triangle was attached to high voltage clamping electrode with the triangular apex pointing axially towards the inlet capillary of the MS system. A 4 kV voltage was then supplied to the electrode, followed by the addition of 2
All experiments were performed using a FLIR Systems AI-MS 1.2 cylindrical ion trap (CIT) mass spectrometer (FLIR Mass Spectrometry, West Lafayette, IN, USA), as previously reported when used in forensic applications [
All analytical scenarios presented herein were examined with both DESI-MS and PSI-MS in positive-ion mode. Pertinent operating conditions for ion collection and focusing via the atmospheric pressure capillary inlet include capillary voltage of 60 V, tube lens voltage of 150 V, and skimmer voltage of 17 V. The inlet capillary of the AI-MS 1.2 is not temperature controlled. Ions were collected via ion gating for 100 ms/scan, and 10 scans/average were utilized for collected spectra.
In order to demonstrate detection capability with the proposed methods, representative positive-ion DESI and PSI-MS data acquired with MS and MS2 scan modes were collected for the target analytes. DESI and PSI-MS data obtained for desomorphine is shown in Figure
Ambient MS analyses of desomorphine on the FLIR Systems AI-MS 1.2. (a) DESI-MS spectrum. (b) DESI-MS/MS of protonated desomorphine. (c) PSI-MS spectrum. (d) PSI-MS/MS of protonated desomorphine.
Ambient MS analyses of codeine on the FLIR Systems AI-MS 1.2. (a) DESI-MS spectrum. (b) DESI-MS/MS of protonated codeine. (c) PSI-MS spectrum. (d) PSI-MS/MS of protonated codeine.
Given the direct analysis capabilities of both DESI-MS and PSI-MS, limits of detection (LODs) were determined for the analysis of surfaces commonly encountered in clandestine synthesis laboratories and as seized paraphernalia (i.e., steel and enamel cookware, PET bottles, and glass). For LOD studies, a 1
Limits of detection (LODs) obtained for the target surfaces studied.
Surface | DESI-MS | PSI-MS | ||
---|---|---|---|---|
Desomorphine | Codeine | Desomorphine | Codeine | |
Printed Teflon slide | 0.50 ng | 0.90 ng | — | — |
Steel | 90 ng | 100 ng | 4.0 ng | 8.0 ng |
Nonstick cookware | 100 ng | 150 ng | 8.0 ng | 10 ng |
Enamel cookware | 200 ng | 200 ng | 2.0 ng | 4.0 ng |
PET bottle | 100 ng | 270 ng | 2.5 ng | 3.5 ng |
Glass | 150 ng | 350 ng | 2.0 ng | 3.0 ng |
In the event of encountering authentic evidence relating to clandestine drug manufacture and distribution, it is quite likely that target analyte(s) will exist as mixtures in potentially complex matrices, such as inactive ingredients found in pharmaceutical precursors, various cutting agents observed in street-level drugs, and contaminants stemming from nonsterile clandestine glassware or storage containers. This is especially the case for the haphazard synthesis of desomorphine, in which there is a high possibility of encountering an incomplete reaction, specifically a slurry containing desomorphine along with unreacted codeine precursor. In order to demonstrate the robustness of the proposed method, multicomponent sample analysis of both substances was demonstrated for both DESI and PSI. Figure
DESI and PSI-MS analysis of a simulated mixture sampled from Teflon-coated cookware. (a) DESI-MS spectrum of 10
A highly desirable capability of on-site evidence screening methods would be to allow direct analysis of authentic forensic evidence with minimal sample preparation. In relation to the synthesis of desomorphine, the codeine precursor is needed as a starting reagent, typically obtained through the extraction of codeine-containing pharmaceutical tablets. To demonstrate the ability to directly screen authentic forensic samples of interest to “Krokodil” production with minimal preparation, DESI and PSI-MS were used to analyze a Tylenol 3 prescription pharmaceutical tablet; the active ingredients in Tylenol 3 are acetaminophen (325 mg) and codeine (30 mg). As seen in Figures
(a) DESI-MS spectrum of a Tylenol 3 tablet, giving rise to protonated acetaminophen and codeine. (b) PSI-MS spectrum of Tylenol 3. (c) MS/MS spectrum of protonated acetaminophen. (d) MS/MS spectrum of protonated codeine.
DESI and PSI-MS ionization sources were coupled with a portable ion trap mass spectrometer to demonstrate the direct analysis capabilities of desomorphine and its precursor codeine. The validity of this method was evaluated through the analysis of trace-level surface-bound residues, yielding low- to sub-ng detection limits from several substrates common to clandestine synthesis. Characteristic fragmentation similar to those reported in the literature and obtained on high-resolution MS instrumentation was achieved, providing confirmation of the target analytes. Due to the varying nature of forensic evidence with regard to chemical complexity, the applicability of the proposed method to multicomponent sample analysis was demonstrated, yielding high chemical specificity. Analysis of an authentic source of codeine precursor (in the form of prescription pharmaceutical tablets) was also demonstrated, supporting the proposed method’s ability of directly analyzing forensic evidence with minimal sample preparation.
The opinions, findings, and conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect those of the Department of Justice.
The authors declare that there are no conflicts of interest regarding the publication of this paper.
This project was supported by Award nos. 2011-DN-BX-K552 and 2015-IJ-CX-K011, awarded by the National Institute of Justice, Office of Justice Programs, U.S. Department of Justice. Molecular assignments for fragmentation spectra were made for select compounds with assistance from high resolution MS instrumentation acquired through support by the National Science Foundation MRI Program under Grant no. CHE 1337497.