By Kevin Shanks, M.S., D-ABFT-FT

Novel psychoactive substances (NPS) come in different varieties – opioids, cannabinoids, stimulants, hallucinogens, and benzodiazepines are just a few of the families on the illicit drug market. Axis developed the Novel Emerging Compounds (NEC) Panel to help detect the most newly emerged NPS on the drug market. The panel is meant to continually evolve in scope as new substances emerge on the street and then either continue to be prevalent or possibly disappear from the market.  

This is intended to be a series of multiple posts briefly describing the compounds in the current iteration of the NEC Panel. 

In the recent past, we have seen the emergence of NPS benzodiazepines such as etizolam, clonazolam, and flualprazolam. In this first summary of the NEC Panel, we are looking at two of the more recently emerged compounds are bromazolam and flubromazepam. 

Bromazolam is a drug that has a history in pharmaceutical drug development as it was first synthesized in the 1970s as XLI-268, but it was never approved for medicinal use. The first emergence of bromazolam on the illicit drug market in the United States was in 2019, but it never became prevalent until more recently. The substance is the brominated analog of alprazolam, meaning it has a bromine atom in the place of the typical chlorine atom.  

Chemical Structure Comparison of Alprazolam and Bromazolam  Structures drawn by Kevin G. Shanks (2023).

Flubromazepam is a drug that also has a history in pharmaceutical drug development. It was first synthesized in 1960, but it did not receive any further study as a medicine. It appeared on the illicit drug market in 2012, but didn’t gain any traction for several years. Flubromazepam is a fluorinated analog of phenazepam, a benzodiazepine used as a medicine in Russia, meaning it has a fluorine atom in the place of the typical chlorine atom. 

Chemical Structure Comparison of Phenazepam and Flubromazepam. Structures drawn by Kevin G. Shanks (2023).

Similar to other classical benzodiazepines such as alprazolam (Xanax), diazepam (Valium), or clonazepam (Klonopin), these compounds act pharmacologically as GABA (gamma-amino butyric acid) receptor agonists. They bind to the GABA receptor and initiate a change in chloride ion channels which leads to inhibition in the central nervous system. Common adverse effects reported by users of NPS benzodiazepines are consistent with those reported after using the classical benzodiazepines and include drowsiness, tiredness, sedation, loss of motor coordination, slurred speech, amnesia, and respiratory depression. Both bromazolam and flubromazepam are not considered controlled substances by the United States Federal government, but may be controlled at a state level as Schedule I controlled substances. Data from the Drug Enforcement Administration’s (DEA) National Forensic Laboratory Information System in 2022 showed that bromazolam was now in the top 15 reported tranquilizers and depressants in the United States. Both bromazolam and flubromazepam have been previously implicated in human intoxication cases involving driving motor vehicles as well as being involved in toxicity leading to fatality. 

Axis qualitatively monitors both of these compounds in our NEC panel (order code 13710) and Comprehensive Panel, Blood with Analyte Assurance (order code 70510) using liquid chromatography with quadrupole time of flight mass spectrometry (LC-QToF-MS). Over the time range 01/30/2023 – 06/30/2023, Axis has detected flubromazepam in 3 blood specimens across 3 states (Indiana, Ohio, and South Dakota) and bromazolam in 72 blood specimens across 15 states (California, Colorado, Florida, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Missouri, Nebraska, Ohio, Tennessee, Texas, and Wisconsin). Bromazolam was commonly detected alongside fentanyl/norfentanyl (n=59), 4-ANPP (n=46), acetylfentanyl (n=27), THC/THC-COOH (n=21), methamphetamine (n=20), and cocaine/benzoylecgonine (n=19). Flubromazepam was typically detected alongside gabapentin/pregabalin (n=3) and fentanyl (n=2). 

Axis also monitors other NPS benzodiazepines in our Novel Psychoactive Substances panel (order code 13610). These additional compounds include adinazolam, clonazolam, etizolam, flualprazolam, and flubromazolam. As always, if you have questions about these substances and how they may apply to your toxicology casework or investigation, please reach out to our subject matter experts by email ([email protected]) or phone (317-759-4869, Option 3).  

Stay tuned for the second post in the NEC Panel series – where we will take a look at two of the more recently emerged stimulant compounds: alpha-PiHP and N,N-dimethylpentylone. 

By Stuart Kurtz, D-ABFT-FT

In April, I spoke at the Midwest Association of Toxicology and Therapeutic Drug Monitoring (MATT) annual conference in Columbus, OH. The title of the talk was “Detection of Xylazine in Postmortem Specimens With Fentanyl, Morphine, Methamphetamine, and Cocaine From 2021-2022.” The conference was a great opportunity to talk shop with peers from the Midwest region and hear what they are doing. In this post, I will summarize what was presented at the MATT conference. 

Xylazine was first synthesized as an antihypertensive by Bayer in 1962. During clinical trials, it was found to have additional central nervous system (CNS) depression effects. Despite being investigated for use as an antihypertensive agent, some patients would initially experience hypertension before the desired effect of a reduction of blood pressure. Some patients also experienced much more severe hypotension than intended. Due to these findings, it was rejected for human medical use and only approved for veterinary purposes. 

A survey done by Texas Poison Control looked at the reported effects of xylazine toxicity. The major reported adverse effects were drowsiness and lethargy (47%), bradycardia (20%), hypotension (11%), hypertension (9%), and slurred speech (8%). Analgesic effects have been reported but the mechanism is not well understood, and the effect is minimal compared to its other adverse effects. There are two theories behind the mechanism. One immunoassay study found that xylazine could weakly displace opioids at binding sites. In this study, naloxone was not seen to reverse the effects. The other theory is that xylazine stimulates the release of endogenous opioids which could be reversed by naloxone. These are theories that have been reported but further study is needed. 

Published case reports involving xylazine typically describe the presence of at least one other additional substance in combination with xylazine which may lead to an additive effect. When xylazine is the primary substance of toxicological interest detected in casework, there is a competing cause of death or an intentional overdose as determined by the scene investigation. The blood concentration range in these cases was 2,300-11,000 ng/mL. In cases of intentional overdose, the decedents worked in the veterinary field and had access to xylazine. The case involving a xylazine blood concentration equal to 2,300 ng/mL was ruled suicide by hanging after injection of xylazine. One attempted suicide case had a serum concentration of 4,600 ng/mL with the individual making a recovery with medical intervention. Two other fatal cases involving xylazine had blood concentrations of xylazine (200 ng/mL)/nordiazepam (2,500 ng/mL)/ and xylazine (300 ng/mL)/flualprazolam (1,100 ng/mL). In driving under the influence of drugs (DUID) casework, a range of 5.1-450 ng/mL of xylazine in blood was found. Full case histories were not available so it is unknown if any of those individuals died from effects of xylazine with other drugs that may have been present. A case of 570 ng/mL in blood was reported from a driver who passed out in their car but could be awakened. 

A heat map of xylazine detections based on data from Axis Forensic Toxicology’s lab.

For the years 2021-2022, we had 442 total detections of xylazine. For reference, we receive about 22,000-24,000 cases per year. The following drugs were commonly detected alongside xylazine: fentanyl (92%), benzoylecgonine (29%), methamphetamine (26%), morphine (12%). In 26% of the cases, the combination of xylazine, fentanyl, and methamphetamine was observed, while in 4% of the cases, the combination of xylazine, fentanyl, methamphetamine, and benzoylecgonine was detected. 

Xylazine detections by quarter have risen slightly since Q1 2021.

64% of xylazine detections fall in the concentration range of 10-40 ng/mL.

Because of the lack of data surrounding human clinical use of xylazine and the lack of reports of sole xylazine use, it is hard to determine what postmortem blood concentrations could be considered fatal. Xylazine is almost always found in combination with another drug due to its popular use as an adulterant. Its CNS depression effects can mimic other compounds such opioids and benzodiazepines and it is not scheduled as a controlled substance by the Drug Enforcement Administration (DEA) in the United States, so access is not very restricted. Because of its additive effects with other CNS depressants, it can still be relevant in postmortem toxicology, and it is included in our comprehensive panel of testing. 

Wounds associated with xylazine use have been reported in Philadelphia, PA. We have not received any reports of wounds potentially associated with xylazine use. Also, in talking with other forensic toxicologists around the country, we have not heard from them any other reports of these wounds being present in their locations. 

As always, please reach out to us if you have any questions about this post. We can be emailed at [email protected] or you can call us at 317-759-4869 option 3. 

Sherri L Kacinko, Amanda L A Mohr, Barry K Logan, Edward J Barbieri, Xylazine: Pharmacology Review and Prevalence and Drug Combinations in Forensic Toxicology Casework, Journal of Analytical Toxicology, Volume 46, Issue 8, October 2022, Pages 911–917, https://doi.org/10.1093/jat/bkac049 

Karla A. Moore, Mary G. Ripple, Saffia Sakinedzad, Barry Levine, David R. Fowler, Tissue Distribution of Xylazine in a Suicide by Hanging, Journal of Analytical Toxicology, Volume 27, Issue 2, March 2003, Pages 110–112, https://doi.org/10.1093/jat/27.2.110 

Malayala SV, Papudesi BN, Bobb R, Wimbush A. Xylazine-Induced Skin Ulcers in a Person Who Injects Drugs in Philadelphia, Pennsylvania, USA. Cureus. 2022 Aug 19;14(8):e28160. doi: 10.7759/cureus.28160. PMID: 36148197; PMCID: PMC9482722. 

Way Koon, Teoh & Muslim, Noor & Chang, Kah Haw & Abdullah, Ahmad Fahmi Lim. (2022). Abuse of Xylazine by Human and its Emerging Problems: A Review from Forensic Perspective. Malaysian Journal of Medicine and Health Sciences. 18. 190-201. 10.47836//mjmhs18.4.26. 

By Stuart Kurtz, M.S. D-ABFT-FT

As discussed in the previous blog post, vitreous humor has many caveats when interpreting its results in the context of postmortem toxicology. For those considerations and some background on vitreous humor, check out that post first (https://axisfortox.com/vitreous-chemistries-pt1). 

Vitreous humor can be used in instances where a drug or dug metabolite is quickly eliminated from the blood and it is known to cross into the vitreous and be detectable. One such metabolite is 6-acetylmorphine (6-AM) which is a marker for heroin exposure. Heroin is not typically looked for in blood samples because of its extremely short half-life at around 5-10 minutes. It metabolizes into 6-AM, which has a longer half-life at around 30 minutes, but it still may not be detectable in blood. Once 6-AM metabolizes into morphine, it is impossible to determine pharmaceutical morphine vs. heroin as the source. Urine would be the best matrix to look for the presence of 6-AM but vitreous humor is also a good option if urine isn’t available. 

Electrolytes testing is one of the most common uses for vitreous humor. This usually includes sodium, potassium, chloride, glucose, urea nitrogen, and creatinine. Sodium and chloride concentrations in vitreous will approximate serum concentrations. Potassium concentrations will rapidly increase postmortem. Urea nitrogen and creatinine are similar to sodium and chloride in terms of correlation with serum concentrations and can be used as indicators for dehydration. Glucose concentrations in vitreous are more reliable than blood glucose concentrations prior to death. However, glucose vitreous concentrations dissipate rapidly in the postmortem interval. Therefore, although a diagnosis of hyperglycemia may be made from elevated vitreous glucose concentrations, a diagnosis of hypoglycemia cannot be made because of the time rate disappearance of glucose from the matrix. Postmortem blood glucose concentrations are considered unreliable and vitreous should be used when possible. 

The significance of vitreous glucose is in helping to determine if diabetes played a part in cause of death. Elevated vitreous glucose is a good indicator that someone was experiencing a diabetic event. This can often be corroborated with acetone presence in the blood and/or vitreous humor. Additional testing for beta-hydroxybutyrate (BHB) can be done in blood if a diabetic event is suspected. Diabetes tends to not have any signs at autopsy so blood and vitreous testing can be helpful. BHB is the primary ketone that is produced during ketoacidosis. Diabetic ketoacidosis is typically associated with elevated glucose in vitreous humor. Medical history can also be very important if vitreous volume is limited or unobtainable. 

The presence of acetone and normal glucose can be an indicator of some other form of ketoacidosis. Alcoholic ketoacidosis may occur in cases of binge drinking alcoholic beverages. As is typical with chronic alcoholism, the person will have evidence of liver disease. The underlying cause is malnourishment which can also occur independently of alcoholism. Malnourishment may also be associated with dehydration which would be indicated by elevated urea nitrogen, sodium, and chloride concentrations. Ultimately, diabetic vs. alcoholic vs. malnourishment ketoacidosis requires additional information beyond just the toxicology testing. 

Medical history and an autopsy are very important for contextualizing the results we can provide for you in these cases. If your case potentially involves dehydration, it may be prudent to check the vitreous for sodium, potassium, or chloride, whereas if your case involves potential issues with diabetes or diabetic ketoacidosis, it would be necessary to order testing for vitreous chemistries to include glucose.  If kidney function is a potential area of concern, evaluation of urea nitrogen and creatinine would be important. Again, as always in forensic toxicology, case circumstances and underlying pathology will aid in determining the best course of action when considering vitreous humor chemistry and electrolytes testing. 

Please reach out to us if you have any questions regarding this topic or want help with deciding what testing may be necessary. Our email is [email protected] and our phone number is 317-759-4869 option 3. 

References 

Guidelines for the Interpretation of Analytical Toxicology Results. Disposition of Toxic Drugs and Chemicals in Man. Twelfth Edition. Randall C. Baselt. Biomedical Publications. Pages xxx-xlii. (2020).  

Introduction to Forensic Toxicology. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 1-12. (2008).  

Postmortem Toxicology. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 191-218. (2008).  

Postmortem Forensic Toxicology. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. AACC, Inc. Pages 3-14. (2017). 

By Stuart Kurtz, M.S. D-ABFT-FT

The purpose of these next two blog posts is to discuss the utility that vitreous humor provides in the context of a case. This first post will focus on what vitreous humor is and the caveats associated with its interpretation. The second post will discuss some scenarios in which it can be very useful. 

Vitreous humor is the fluid found in the eyes between the lens and retina. There is approximately 2 mL of fluid in each eye meaning the volume is limited for testing. Because of this, we don’t recommend the use of vitreous humor as the primary specimen, and we do recommend careful consideration before attempting testing on it. The context of the case is always important and sometimes that is the most useful sample to test. Therefore, from a whole case investigation approach, we recommend always collecting vitreous humor, alongside blood and/or urine, at autopsy – if possible. Collection should be done in a tube without sodium fluoride or potassium oxalate as a preservative. The clear top tubes that are provided in our toxicology kits are well suited for vitreous collection, having no preservatives.

The primary components of vitreous humor are a connective tissue gel and transparent liquid that is primarily water. Its composition and location mean that it is quite stable and resistant to putrefactive changes postmortem. Movement of substances in and out of the vitreous happens by diffusion, osmotic pressure, convection, or active transport. Low molecular weight substances, such as ethanol, acetone, methanol and isopropanol, will travel in and out via diffusion. Most drugs that are important in postmortem testing are a much higher molecular weight and will travel in and out via convection. 

Ultimately, the mechanisms for most substances entering the vitreous are mostly unknown and/or not well studied. Drugs such as fentanyl, methamphetamine, and cocaine might be found in vitreous humor but the ability to correlate to a blood concentration is extremely limited and not recommended. Most drugs are very fat soluble and the vitreous humor is mostly water. So just like with oil and water, drugs will not be easily dissolved in the small volume present. 

Whereas with urine we expect that the majority of drugs will be found there in one form at some point post-exposure, that may not be the case with vitreous humor. There may be some drugs that are so poor in their ability to enter the vitreous humor that they would be undetectable. It can have some ability to show recent exposure, similar to urine, of a drug, but the absence of a drug should be interpreted with caution. 

Our next post will discuss vitreous humor’s important use in forensic toxicology. As always, we are here to assist you. Please reach out to us if you have any questions regarding this topic or want help with deciding what testing may be necessary. Our email is [email protected] and our phone number is 317-759-4869 option 3. 

References 

Guidelines for the Interpretation of Analytical Toxicology Results. Disposition of Toxic Drugs and Chemicals in Man. Twelfth Edition. Randall C. Baselt. Biomedical Publications. Pages xxx-xlii. (2020).  

Introduction to Forensic Toxicology. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 1-12. (2008).  

Postmortem Toxicology. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 191-218. (2008).  

Postmortem Forensic Toxicology. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. AACC, Inc. Pages 3-14. (2017). 

The purpose of this blog post is to take a look at some of our data regarding nitazene detections. For some background on nitazene compounds, take a look at our blog post of June 9, 2022 titled Drug Primer: Nitazenes. As a reminder, nitazenes are a structurally distinct class of opioids so non-specific tests such as color strips and immunoassays will not detect them. 

For the SOFT 2022 meeting in Cleveland, Stuart Kurtz presented a poster titled Emergence of the Nitazene Class of Novel Synthetic Opioids in Postmortem Toxicology and Detection by LC-QToF-MS that looked at areas of detection as well as compounds found with nitazenes. Since that presentation, we examined the data through Q4 in 2022 to see what trends, if any, we could see in our casework. A big caveat is that the number of detections is a product of the testing being ordered. Nitazene screening is done as part of the comprehensive panel and not every case has comprehensive testing ordered. 

One of the main takeaways from the poster was that only 11 out of the 128 cases examined had a nitazene present with no detection of fentanyl, morphine, methamphetamine, or cocaine. 83% of the cases had fentanyl detected with a nitazene. This is consistent with the trend of polysubstance overdose deaths rising and fentanyl being the dominate opioid detected. 

Metonitazene was most commonly detected (n=102) with a big drop off to isotonitazene (n=22). Flualprazolam was the most common non-opioid NPS detected. Detection of opioids and NPS benzodiazepines has been an increasing trend in seized materials. Non-NPS detected included diphenhydramine (n=23) and gabapentin (n=16) which are suspected as cutting agents. It’s impossible to tell from postmortem toxicology work if a substance was cut with something but seized material data suggests that these are common cutting agents. Xylazine (n=7) has emerged as a common cutting agent and is gaining popularity in media. We will have more on xylazine in a future post. It is important to note that the presence of diphenhydramine or gabapentin does not necessarily mean they are a cutting agent since they are available over-the-counter and with a prescription respectively. Medical and prescription history is important in helping to determine where they may have come from. 

The data from the SOFT poster was from June 2021 through May 2022. We went back and looked at the data through the end of 2022 to see if there were any trends regarding detection. We didn’t look at other drugs detected as we feel the sampling for the SOFT poster represents general trends well. We did see that the detections of nitazenes peaked in Q1 of 2022 and has dropped off through the end of 2022. 

We updated the heat map regarding number of detections in each state. Keep in mind that Axis does not necessarily service the entirety of a state so actual numbers may be higher than what is shown. Indiana (n=130) is the leader in detections from our data. While the compounds that we test for may not be detected as often, that doesn’t mean that nitazenes as a class have completely disappeared. 

The NPS landscape is always changing and requires us to adapt our testing scope. The best information we can have to help inform testing is testing unknown powders at the scene. A powder at a scene doesn’t mean that the person was exposed to it but it can be a big help in knowing what to look for and guiding you on future testing. The next best piece of information is knowing what is being found in seized materials in the region. Again, this doesn’t guarantee that a person was exposed to the NPS but helps make us aware of what we may need to test for. 

As always, please feel free to reach out to us with any questions either by phone at 317-759-4869 option 3 or by email at [email protected]. 

In October, toxicologist Stuart Kurtz presented a poster at the annual National Association of Medical Examiners (NAME) meeting in Dallas, TX. The abstract is below.

A Case Report Involving the Detection of Five New Psychoactive Substances in Postmortem Analysis.  

Stuart A. K. Kurtz, MS (1), Billy Scott (2), George S. Behonick, Ph.D., F-ABFT (1), and Kevin G. Shanks (1), MS, D-ABFT-FT 

(1) Axis Forensic Toxicology, Indianapolis, IN, USA; (2) Clark County Coroner, Jeffersonville, IN, USA 

Scheduling of fentanyl analogs in recent years has created a shift in new synthetic opioids (NSO) that are being detected by drug and toxicology laboratories. While the detection of fentanyl analogs has decreased, other NSOs have risen to fill the space. The intention of these NSOs is to mimic the effects on the body of prescription medications and previously available illicit drugs. They are often drugs that were synthesized by pharmaceutical companies in the mid-1900s, but studies were halted leaving a gap in information as to how the drugs behave pharmokinetically and pharmacodynamically. The constant emergence of these compounds creates detection challenges for laboratories, medical examiners, and coroners. Flualprazolam, a designer benzodiazepine, has also emerged in recent years in the illicit drug market. This case report involves the detection of four NSOs (brorphine, fluorofentanyl, flunitazene, metonitazene) with three different class types (benzimidizol-2-one, fentanyl analog, nitazene analog) and a designer benzodiazepine (flualprazolam). 

Jugular blood was submitted for toxicological analysis. The screen utilizes an extraction followed by high resolution mass spectrometry via liquid chromatography quadrupole time of flight mass spectrometry (LC-QToF-MS). Novel psychoactive substance subclasses screened for include NSOs, designer benzodiazepines, synthetic cathinones (bath salts), and synthetic cannabinoids. Toxicological findings include methamphetamine (245 ng/mL), fentanyl (40.1 ng/mL), norfentanyl (3.3 ng/mL), and the qualitative presence of cotinine, quinine, 4-ANPP, brorphine, fluorofentanyl, flunitazene, and metonitazene. 

There are a few things I would like to highlight here. The first is the instrumentation that we use to identify compounds of interest in a sample. We use liquid chromatography paired with a quadrupole and time-of-flight mass spectrometer (LC-QToF-MS). This allows us to collect data in such a way that we can go back and reprocess the data to see if something is present in the sample. 

The second thing is the whack-a-mole game that is ongoing when it comes to identifying these NPS compounds. The lifecycle of an NPS in the drug supply is often determined by government scheduling of either the NPS itself or the materials that are used to synthesize it. They can show up abruptly and gradually begin to replace one or more compounds. An example of this is the emergence of flualprazolam and isotonitazene mixtures in 2019. The scheduling of isotonitzene led to the emergence of brorphine in that mixture in 2020. 

Thirdly, detection of NPS in post-mortem casework can have a lag time of weeks to months depending on the intelligence data available. Information that can greatly improve our ability to upgrade our testing to including compounds of interest is scene data. Testing the unknown substances at the scene is the best way to determine what to look for. The data from the LC-QToF-MS can be processed to look for compounds that were previously not monitored in our methods. However, this is best done when there is the identification of something specific in seized drugs in a jurisdiction but is even more precise with scene identification of a compound. 

Lastly, it is important to utilize identification techniques that are specific. These include LC-QToF-MS, liquid chromatography paired with triple quadrupole mass spectrometry, and gas chromatography paired with mass spectrometry. These techniques are significantly less prone to false positives and false negatives. The methods that use these techniques often go through rigorous validation to show what the limits are to prevent false positives and false negatives. Less specific techniques such as immunoassays, color tests, and test strips are prone to false positives and false negatives. These types of tests tend to rely on core structures and/or functional groups. The core structure of morphine is different from fentanyl so one of these non-specific tests that work for morphine may not be able to detect fentanyl. 

There were 5 different portions of powder collected at the scene. A plastic baggy and folded up receipt were described to contain a blackish/grayish substance. 3 additional folded up receipts were collected and described to contain white powders. Brorphine and flualprazolam are often seen together in seized drug material and sometimes known as “benzo dope.” Metonitazene and flunitazene were also identified with flualprazolam in our casework. We do not have any information on whether they were mixed with the flualprazolam and consumed. A limitation of toxicology testing is it does not tell you if something was consumed in the same mixture as something else. The wider investigation would have to determine if that was a possibility. The MOD and COD were determined to be accidental due to methamphetamine and fentanyl toxicity. The methamphetamine level was 245 ng/mL and the fentanyl level was 40.1 ng/mL. 

As always, please reach out to us with questions. We are happy to help guide toxicology testing and interpretation however we can. 

Keary CJ, Wang Y, Moran JR, Zayas LV, Stern TA. Toxicologic testing for opiates: understanding false-positive and false-negative test results. Prim Care Companion CNS Disord. 2012;14(4):PCC.12f01371. doi: 10.4088/PCC.12f01371. Epub 2012 Jul 26. PMID: 23251863; PMCID: PMC3505132. 

Marthe M Vandeputte, Alex J Krotulski, Donna M Papsun, Barry K Logan, Christophe P Stove, The Rise and Fall of Isotonitazene and Brorphine: Two Recent Stars in the Synthetic Opioid Firmament, Journal of Analytical Toxicology, Volume 46, Issue 2, March 2022, Pages 115-121, https://doi.org/10.1093/jat/bkab082 

Truver MT, Chronister CW, Kinsey AM, Hoyer JL, Goldberger BA. Toxicological Analysis of Fluorofentanyl Isomers in Postmortem Blood. J Anal Toxicol. 2022 Mar 11:bkac014. doi: 10.1093/jat/bkac014. Epub ahead of print. PMID: 35277721. 

The Center for Forensic Science Research & Education. 2022 Q2 NPS Opioids Trend Report. https://www.npsdiscovery.org/wp-content/uploads/2022/07/2022-Q2_NPS-Opioids_Trend-Report.pdf 

Blanckaert, P, Balcaen, M, Vanhee, C, et al. Analytical characterization of “etonitazepyne,” a new pyrrolidinyl-containing 2-benzylbenzimidazole opioid sold online. Drug Test Anal. 2021; 13( 9): 1627– 1634. https://doi.org/10.1002/dta.3113 

Sara E Walton, Alex J Krotulski, Barry K Logan, A Forward-Thinking Approach to Addressing the New Synthetic Opioid 2-Benzylbenzimidazole Nitazene Analogs by Liquid Chromatography–Tandem Quadrupole Mass Spectrometry (LC–QQQ-MS), Journal of Analytical Toxicology, Volume 46, Issue 3, April 2022, Pages 221–231, https://doi.org/10.1093/jat/bkab117 

If you would like a copy of the poster, please email [email protected].