Review: Rapid Detection of Fentanyl, Fentanyl Analogues, and Opioids for On-Site or Laboratory Based Drug Seizure Screening Using Thermal Desorption DART-MS and Ion Mobility Spectrometry

Emily C. Lennert





opioid, heroin, fentanyl, carfentanil, analogues, drug, thermal desorption, direct analysis in real time, mass spectrometry, DART-MS, TD-DART-MS, ion mobility spectrometry, IMS

Article Reviewed

  1. Sisco, E.; Verkouteren, J.; Staymates, J.; Lawrence, J. Rapid detection of fentanyl, fentanyl analogues, and opioids for on-site or laboratory based drug seizure screening using thermal desorption DART-MS and ion mobility spectrometry. Forensic Chemistry. 2017, 4, 108-115.


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.


Opioid abuse increasingly problematic in the U.S., and handling of drug evidence now poses a threat to law enforcement, first responders, medical personnel, and forensic analysts. Fentanyl and fentanyl analogues, such as carfentanil, are much more potent than regular opioids, such as morphine. This potency makes accidental exposure, such as through seizure of drug evidence, potentially life threatening; possible exposure routes include absorption through skin, inhalation, and ingestion. A dose of fentanyl as low as 2 mg may be lethal, and many analogues are more potent than fentanyl; carfentanil is approximately 100 times more potent than fentanyl. The dangerous nature of these materials makes analysis of drug evidence more difficult, due to the extreme caution that must be exercised in processing possible fentanyl containing evidence. As such, an analysis method that is rapid, sensitive, and safe is desirable. Rapid analysis may be applicable in medical settings, allowing for the proper medical treatment to be determined based on the drug that is present. A sensitive method must allow for sampling of the outside of a container/bag to protect the analyst from sampling the bulk powder, e.g. to prevent exposure. The authors of this study examined two methods for fentanyl and fentanyl analogue analysis: thermal desorption direct analysis in real time – mass spectrometry (TD-DART-MS) and ion mobility spectrometry (IMS). In thermal desorption, a sample is heated to release compounds that have adsorbed to the material. Both instruments are rapid means of analysis, and may be field deployable or used in a traditional laboratory.

A total of 22 opioid compounds were analyzed, listed in Table 1 within the study, and include fentanyl, 16 fentanyl analogues, heroin, and 4 other opioids. Heroin and other opioids were included to determine whether fentanyl and its analogues could be detected in the presence of another opioid, since fentanyl is often mixed with opioids such as heroin. In addition to opioids, 5 excipients, i.e. fillers or cutting agents, were analyzed to determine whether the presence of the cutting agent affected the ability to detect the opioids. Finally, simulants of common background materials were tested for possible interference with opioid detection: fingerprint material, dirt, and plastic bags.

TD-DART-MS samples were examined on polytetrafluroethylene (PTFE) coated fiberglass wipes. An independent thermal desorption unit was coupled with a DART-MS equipped with a Vapur® interface by a glass T-junction. This set-up helps to minimize the analyst’s risk of exposure, versus an open system like in regular DART-MS. IMS samples were analyzed on meta-aramid fiber wipes. Wipes were selected to be representative of real world sampling methods, e.g. wiping the outside of a bag containing suspected opioids. Samples were pipetted directly onto the wipe, allowed to dry, and then inserted directly into each instrument’s thermal desorber unit, where temperatures were set to 255C for TD-DART-MS and 245C for IMS.

TD-DART-MS Detection Results

Samples were analyzed by TD-DART-MS at 4 different orifice 1 voltages: 20, 30, 60, and 90 V. The increasing voltages induce fragmentation. Fragmentation patterns may be used to differentiate compounds that have the same mass. All opioids produced signals, with fragmentation increasing as voltage increased. At low voltages, three sets of fentanyl analogues were not differentiable. The lack of differentiation was due to identical molecular ion peaks, i.e. the compounds had the same m/z. Higher voltages allowed for differentiation by fragmentation of some analogues that were indistinguishable, but not of isomers. Isomers are compounds that share a formula but have different arrangements of atoms within the molecule. The indistinguishable isomers shared identical fragmentation patterns at higher voltages, and were unable to be differentiated. Limits of detection (LOD) were then determined. For all compounds except heroin and buprenorphine, LOD were determined to be below ng/wipe levels, with most analogues detectable at a few hundred pg/wipe.

IMS Detection Results

In most samples, a single distinct peak for the compound was seen by IMS analysis. Five pairs of fentanyl analogues could not be differentiated from one another, as well as one pair of an analogue and an opioid. One pair of isomers was differentiated by IMS that could not be differentiated by TD-DART-MS. LODs for each drug was determined and were approximately equal to the LODs obtained by TD-DART-MS. High sensitivities, i.e. low LOD, indicated the possibility of sampling by wiping the outside of a bag or other surface, rather than sampling of the powder itself, which helps to limit exposure to the drug by the investigator.

Detection in Opioid and Excipient Mixtures

Fentanyl is commonly encountered within a mixture, often with heroin. The authors examined whether the signal of fentanyl would be affected by the presence of heroin or cutting agents: mannitol, acetaminophen, quinine, procaine, and caffeine.


In the presence of heroin, fentanyl showed no decrease in signal, regardless of the ratio of fentanyl:heroin, i.e. 1:1 – 1:1000. In the presence of mannitol, the signal of fentanyl increased as the amount of mannitol increased. Conversely, acetaminophen showed a reduction in the fentanyl signal as the amount of acetaminophen increased. However, fentanyl remained detectable even at a fentanyl:acetaminophen ratio of 1:1000. Quinine and procaine resulted in trends similar to heroin, with slight reduction in fentanyl signal at the 1:1000 level. Caffeine produced similar trends to acetaminophen, although the reduction of the fentanyl signal was smaller.
Additional studies were then conducted using fentanyl analogues and opioids to determine if similar results were obtained for these drugs in the presence of heroin. The analogues studied produced responses similar to that of fentanyl, with the exception of butyryl fentanyl, which showed a 35% reduction in signal.


In the presence of heroin, a “combination” peak occurred during IMS analysis. This peak, shown in Figure 3b within the study, contained the signal for both heroin and fentanyl, exhibiting a lack of resolution between the signals for the two compounds, which showed one peak for both compound instead of two. This lack of resolution, i.e. a combination peak, also occurred in mixtures of heroin with some fentanyl analogues. In the presence of acetaminophen, little suppression of the fentanyl signal was observed. Little suppression was also induced by caffeine; however, the level of suppression in the presence of caffeine increased at the 1:100 level of fentanyl:caffeine, with a 50% reduction in the fentanyl signal. In the presence of mannitol and quinine, the signal of fentanyl was enhanced. Procaine produced complete suppression of the fentanyl signal at levels greater than 1:1.

Detection in Background Contamination Mixtures

Artificial fingerprint residue was used to simulate the presence of fingerprint material in samples containing fentanyl and heroin. The artificial fingerprint residue contained over 40 compounds commonly found in fingerprints at appropriate biological concentrations. After subtraction of the fingerprint material as background, both fentanyl and heroin were easily detected by TD-DART-MS. By IMS, fentanyl was detected; however, heroin was only detected in one of two replicates.

Dirt was simulated using National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 1944. SRM 1944 was suspended in water, then pipetted onto the wipe allowed to dry. Heroin and fentanyl were then added to the wipe and the sample was analyzed by TD-DART-MS or IMS. By TD-DART-MS, both heroin and fentanyl were detected. However, the signal for heroin appeared reduced when compared to the fingerprint sample of the same concentration. By IMS, only fentanyl was detected.

Finally, samples were deposited on a plastic bag. The bag was handled with bare hands to contaminate the bag with real fingerprint residue, then fentanyl and heroin were deposited onto the bag. The bag was then wiped with either the PTFE wipe or meta-aramid wipe, and the wipe was analyzed using the appropriate instrument. Both heroin and fentanyl were detected by TD-DART-MS and IMS. However, some suppression of the signal was observed for the heroin signal under TD-DART-MS analysis, but the fentanyl signal was strong. In IMS, the combination peak for heroin and fentanyl was observed.

Scientific Highlights

  • Highly sensitive detection of fentanyl and fentanyl analogues was achieved using TD-DART-MS and IMS.
  • Fentanyl was detected in a mixture with heroin, down to 0.1% by weight fentanyl, by both instrumental methods.
  • A combination heroin-fentanyl peak was observed on IMS.
  • In the presence of excipients and complex matrices, fentanyl remained detectable by TD-DART-MS. IMS provided similar results; however, the presence of procaine made fentanyl undetectable by IMS. Fentanyl analogues produced similar results to fentanyl.


Opioid abuse, including fentanyl and fentanyl analogues, is a growing epidemic in the U.S. The methods presented provide a means for identification of fentanyl and fentanyl analogues which may be applied in forensic casework.

Potential Conclusions

  • The methods presented provide a means for identification of fentanyl and fentanyl analogues in the presence of various commonly expected compounds, e.g. heroin, acetaminophen, or fingerprint residue.
  • The methods presented allow for the sampling of the outside of a bag containing suspected fentanyl or fentanyl analogues, therefore minimizing risk to individuals processing the evidence, e.g. law enforcement and forensic analysts.