Emily C. Lennert
trace, drug, metabolite, cutting agent, thermal, desorption, direct analysis in real time, DART, mass spectrometry, MS, stimulants, opioids, cannabinoids, synthetic cathinones, hallucinogens, benzodiazepines
- Sisco, E.; Forbs, T. E.; Staymates, M. E.; Gillen, G. Rapid analysis of trace drugs and metabolites using a thermal desorption DART-MS configuration. Analytical Methods. 2016, 8, 6494-6499.
The opinions expressed in this review are an interpretation of the research presented in the article. These opinions are those of the summation author and do not necessarily represent the position of the University of Central Florida or of the authors of the original article.
Swipe sampling is a common method for trace detection of drugs; the method is commonly employed at security checkpoints and requires rapid and selective methods of analysis. Currently, a technique called ion mobility spectrometry (IMS) is commonly used for this purpose; however, the technique lacks specificity for some drugs that have similar chemical compositions, such as synthetic cathinones or cannabinoids. The method presented here is a proof of concept for the use of thermal desorption – direct analysis in real time – mass spectrometry (TD-DART-MS) for the analysis of drug residues, metabolites, and cutting agents from swipe samples. The given method is not optimized, but provides highly sensitive analysis of swipe samples.
DART-MS is a rapid and selective method of analysis. However, sample reproducibility is difficult due to variations in sample introduction. Additionally, traditional DART-MS is not practical for the analysis of swipe samples. Thermal desorption (TD) was selected to allow for analysis of swipe samples. In a TD configuration, the gas stream exiting the DART source is confined in a glass tube. A heated sampling unit, i.e. TD, is attached to the tube as well. The sample is inserted into the TD unit, where substances are thermally desorbed, or released from the sampling surface due to heat. The substances, now desorbed, enter the gas stream within the glass tube and are pushed into the mass analyzer.
A total of 34 drugs, metabolites, and cutting agents were analyzed. A complete listing of samples can be found in table 1 within the study. Each swipe was prepared by depositing 100 ng of the compound on the swipe. Each sample was then individually placed in the sampling slot of the TD, maintained at 240 ˚C, and analyzed. Instrument response was seen rapidly, approximately two seconds after insertion of the sample, with large peaks easily distinguished from the background signal. Samples were analyzed in positive mode. For an explanation of how DART-MS works, refer to Review: Characterizing and Classifying Water-Based Lubricants Using Direct Analysis in Real time®–time of Flight Mass Spectrometry. For 33 of the compounds, a [M+H]+ protonated molecule was easily detected. Only one molecule did not form the protonated molecule; ecgonine methyl ester (EME), a metabolite, produced a [M + H3O]+ molecule. Fragmentation was induced during analysis, with orifice 1 voltages ranging from 10V, 30V, 60V, and 90V. With increasing voltages, most molecules showed a decrease in the molecular ion peak (i.e. the weight of an unfragmented compounds) as fragmentation increased, as expected.
Spectra obtained by TD-DART-MS were then compared to results obtained by traditional DART-MS using the NIST DART Forensics Library. Of the 34 compounds studied, 16 were present in the NIST library. Comparison of spectra obtained by TD-DART-MS and traditional methods, at the same voltages, showed that all observed peaks matched between the spectra.
Limits of detection (LOD), i.e. the lowest quantity that can be detected, for the samples were determined. Spectra obtained at 10V were used, since spectra with fragmentation had reduced base peaks, e.g. the [M + H3O]+ peak in EME and the molecular peak in the remaining 33 compounds. LODs were determined to be less than or equal to 1 ng per swipe sample, and were lower than previously reported for traditional DART-MS. Larger compounds such as heroin were detectable at 5 ng. The authors state that the higher LOD for the larger compounds is likely due to lower volatility of the sample, and that a higher temperature may produce lower LODs. All LODs can be seen in table 1 within the study. A small subset of 3 samples was analyzed via TD-DART-MS and traditional DART-MS. In each instance, TD-DART-MS produce LODs that were lower by a factor of 20 or more as compared to traditional DART-MS. Sample-to-sample variation was also examined, and relative standard deviations (RSD) were calculated to evaluate the variation. TD-DART-MS variation ranged from 5-14% RSD, whereas traditional DAT-MS ranged from 23-80% RSD.
A calibration curve was also produced using the TD-DART-MS configuration to determine quantitative capability. Due to difficulties in reproducibility using traditional DART-MS, quantitative analysis may be challenging. Methylenedioxyamphetamine (MDA) was used to produce a calibration curve, with six different quantities of MDA, one per swipe sample, ranging 1-100 ng. Each quantity was repeated five times, and a calibration curve was created with the resulting data. A linear calibration curve with R2 greater than 0.999 was achieved, indicating a very good calibration curve; a score of 1.0 is indicative of a perfect linear calibration.
Finally, complex mixtures were analyzed. In real world cases, the likelihood that a swipe will contain pure drug is very low. To simulate real samples, four types of complex samples containing trace amounts of the target analytes were prepared. First, samples containing several drugs were created and analyzed. Individual drugs were easily identified within the complex mixtures. Second, samples containing drugs and common cutting agents, such as heroin and acetaminophen, were created and analyzed. Again, each compound was easily identified within the mixture. A third sample type containing Δ9-THC and cannabinol with two metabolites was also analyzed; each compound was easily identified within the mixture. Hand swipes or direct analysis of fingerprints from swipe material may be used in the field. Therefore, a fourth complex mixture of swipe samples containing artificial fingerprint materials and trace drug amounts were prepared. Fingerprint materials did not affect the ability to identify drugs within the samples, and all trace drugs present were identified with ease.
TD-DART-MS was shown in this study to detect trace levels of several drugs, metabolites, and cutting agents with ease. Additionally, the results were reproducible, and a highly linear calibration curve was developed to allow for potential quantification using the TD-DART-MS configuration. Complex mixtures were analyzed with ease. The authors state that further work is being conducted to evaluate TD-DART-MS for use in explosives analysis and other fields.
- 32 drugs, metabolites, and cutting agents were easily and rapidly analyzed from swipe samples by TD-DART-MS.
- TD-DART-MS produced more reliable results compared to traditional DART-MS for the subset of samples analyzed.
- A calibration curve with high linearity, R2 > 0.999, was obtained for MDA, an amphetamine. This suggests that TD-DART-MS may provide an accurate quantification method for drug analysis.
- Presence of a complex sample matrix did not impact the ability to identify analytes by TD-DART-MS.
DART-MS allows for rapid analysis of samples, with sample spectra being observable within seconds of sample introduction. However, the technique may suffer from poor reproducibility between samples. The TD-DART-MS configuration provides a more reproducible method for DART analysis.
- Accurate quantification may be possible with TD-DART-MS.
- TD-DART-MS may allow for more reproducible analysis compared to DART-MS.