Assessment of two brands of fentanyl test strips with 251 synthetic opioids reveals "blind spots" in detection capabilities.

BACKGROUND: Fentanyl test strips (FTS) are a commonly deployed tool in drug checking, used to test for the presence of fentanyl in street drug samples prior to consumption. Previous reports indicate that in addition to fentanyl, FTS can also detect fentanyl analogs like acetyl fentanyl and butyryl fentanyl, with conflicting reports on their ability to detect fentanyl analogs like Carfentanil and furanyl fentanyl. Yet with hundreds of known fentanyl analogs, there has been no large-scale study rationalizing FTS reactivity to different fentanyl analogs. METHODS: In this study, 251 synthetic opioids-including 214 fentanyl analogs-were screened on two brands of fentanyl test strips to (1) assess the differences in the ability of two brands of fentanyl test strips to detect fentanyl-related compounds and (2) determine which moieties in fentanyl analog chemical structures are most crucial for FTS detection. Two FTS brands were assessed in this study: BTNX Rapid Response and WHPM DanceSafe. RESULTS: Of 251 screened compounds assessed, 121 compounds were detectable at or below 20,000 ng/mL by both BTNX and DanceSafe FTS, 50 were not detectable by either brand, and 80 were detectable by one brand but not the other (n = 52 BTNX, n = 28 DanceSafe). A structural analysis of fentanyl analogs screened revealed that in general, bulky modifications to the phenethyl moiety inhibit detection by BTNX FTS while bulky modifications to the carbonyl moiety inhibit detection by DanceSafe FTS. CONCLUSIONS: The different "blind spots" are caused by different haptens used to elicit the antibodies for these different strips. By utilizing both brands of FTS in routine drug checking, users could increase the chances of detecting fentanyl analogs in the "blind spot" of one brand.

Costing analysis of a point-of-care drug checking program in Rhode Island.

BACKGROUND: Drug checking is a harm reduction strategy that provides greater awareness and information about the drug supply to the community. While fentanyl test strips are low-cost and available in most parts of the U.S., community-based organizations are considering using more sophisticated technologies, such as Fourier-transform infrared (FTIR) spectroscopy to test drugs. FTIR can detect multiple substances in a non-destructive manner that can be rapidly communicated to the program client by a trained technician, however implementation costs in community-based settings have not been assessed. METHODS: We conducted a costing analysis of a new pilot drug checking service that employed an FTIR spectrometer, fentanyl test strips and confirmatory testing in Rhode Island from January 2023-May 2023. We used microcosting methods to determine the overall cost during this period and cost per drug checked, reflecting realistic service capacity. RESULTS: Among 101 drug samples that were voluntarily submitted and tested, 53% tested positive for fentanyl, 39% for cocaine, 9% for methamphetamine and 13% for xylazine, a powerful sedative. The total cost during this period was $71,044 and the cost per drug checked was $474, though sensitivity analyses indicated that the cost would rise to $78,058 - $83,058 or $544 - $593 for programs needing to pay for specialized training. CONCLUSIONS: These findings demonstrate feasibility and inform the resources needed to scale-up drug checking services to reduce overdose risk.

A qualitative assessment of key considerations for drug checking service implementation.

BACKGROUND: With many drug-related deaths driven by potent synthetic opioids tainting the illicit drug supply, drug checking services are becoming a key harm reduction strategy. Many drug checking technologies are available, ranging from fentanyl test strips to mass spectrometry. This study aimed to identify key considerations when implementing drug checking technologies and services to support harm reduction initiatives. METHODS: Key informant interviews were conducted with harm reduction stakeholders throughout Illinois. Participants included members of existing drug checking services and recovery centers. Interviews were recorded, transcribed, and coded by two researchers using the framework method. Findings were contextualized according to micro (client)-, meso (organization)-, and macro (policy)-level themes. RESULTS: Seven interviews were conducted with ten participants. Fourier transform infrared spectroscopy was consistently identified as a technology of choice given its accuracy, range of substance detection, portability, and usability. Recommendations included the use of confirmatory testing, which can help address the limitations of technologies and provide a mechanism to train technicians. Locations of drug checking services should maximize public health outreach and leverage existing harm reduction agencies and staff with lived experience, who are critical to developing trust and rapport with clients. Criminalization and loss of privacy were major concerns for clients using drug checking services. Additional issues included the need to raise awareness of the legitimacy of services through public support from governing bodies, and funding to ensure the sustainability of drug checking services. CONCLUSIONS: This research facilitated the identification of issues and recommendations from stakeholders around key considerations for the adoption of drug checking technologies, which not only included the cost and technical specifications of instrumentation, but also broader issues such as accessibility, privacy, and well-trained personnel trusted by clients of the service. Successful implementation of drug checking services requires knowledge of local needs and capacity and an in-depth understanding of the target population.

Metonitazene in the United States-Forensic toxicology assessment of a potent new synthetic opioid using liquid chromatography mass spectrometry.

Metonitazene is considered a new psychoactive substance (NPS) and emerging potent synthetic opioid, causing increased public health concern beginning in 2020. Metonitazene joins a growing list of new synthetic opioids (NSOs) contributing to deaths among people who use drugs in the United States and other parts of the world. Metonitazene (a 2-benzylbenzimidazole analogue) first appeared in mid-2020 in the recreational drug supply and subsequently began proliferating in death investigation casework towards the end of 2020. Screening and metabolite discovery were performed by liquid chromatography quadrupole time-of-flight mass spectrometry. Quantitative confirmation was performed by liquid chromatography tandem quadrupole mass spectrometry. Metonitazene was confirmed in 20 authentic forensic postmortem cases with an average concentration in blood at 6.3 ± 7.5 ng/ml (median: 3.8 ng/ml, range: 0.5-33 ng/ml, n = 18) and in urine at 15 ± 13 ng/ml (median: 11 ng/ml, range: 0.6-46 ng/ml, n = 14). Metonitazene was the only opioid identified in 30% of cases but was also found in combination with fentanyl (55%) and NPS benzodiazepines, opioids, and hallucinogens (45%). Medical examiners included metonitazene as a drug responsible for the cause of death, and the manner of death was always ruled to be an accident. The metabolism of metonitazene was found to be similar to that of isotonitazene, a closely related analogue. Toxicology laboratories and death investigators should ensure that metonitazene is included in forensic testing protocols, all while remaining vigilant for subsequent NSOs to emerge.

An assessment of the limits of detection, sensitivity and specificity of three devices for public health-based drug checking of fentanyl in street-acquired samples.

BACKGROUND: Fentanyl has caused rapid increases in US and Canadian overdose deaths, yet its presence in illicit drugs is often unknown to consumers. This study examined the validity in identifying the presence of fentanyl of three portable devices that could be used in providing drug checking services and drug supply surveillance: fentanyl test strips, a hand-held Raman Spectrometer, and a desktop Fourier-Transform Infrared Spectrometer. METHODS: In Fall 2017, we first undertook an assessment of the limits of detection for fentanyl, then tested the three devices' sensitivity and specificity in distinguishing fentanyl in street-acquired drug samples. Utilizing test replicates of standard fentanyl reference material over a range of increasingly lower concentrations, we determined the lowest concentration reliably detected. To establish the sensitivity and specificity for fentanyl, 210 samples (106 fentanyl-positive, 104 fentanyl-negative) previously submitted by law enforcement entities to forensic laboratories in Baltimore, Maryland, and Providence, Rhode Island, were tested using the devices. All sample testing followed parallel and standardized protocols in the two labs. RESULTS: The lowest limit of detection (0.100 mcg/mL), false negative (3.7%), and false positive rate (9.6%) was found for fentanyl test strips, which also correctly detected two fentanyl analogs (acetyl fentanyl and furanyl fentanyl) alone or in the presence of another drug, in both powder and pill forms. While less sensitive and specific for fentanyl, the other devices conveyed additional relevant information including the percentage of fentanyl and presence of cutting agents and other drugs. CONCLUSION: Devices for fentanyl drug checking are available and valid. Drug checking services and drug supply surveillance should be considered and researched as part of public health responses to the opioid overdose crisis.

Post-mortem analysis of prescription opioids-A follow-up examination by LC-MS/MS with focus on fentanyl.

Our aim was to investigate the reason for relatively low detection rates for opioids and fentanyl in particular in post-mortem cases in the State of Hamburg. We re-analysed 822 blood samples from two different time periods, 2011/12 and 2016. These samples had been previously analysed in accordance with post-mortem routine by a case selected strategy. All samples were re-analysed with an LC-MS/MS method specific for prescription opioids. The main point in the evaluation was to determine whether the previous analysis strategy had led to underreporting of drug-related deaths (DRD), especially with regard to fentanyl. Another aim was to evaluate changes in prescribing prevalence of opiates and opioids. We compared pharmacy claims data in Hamburg with Germany. The analyses showed that the number of DRD remained unaffected by the new analytical strategy. Detection rates in DRD, however, increased for fentanyl 3.4-fold from 1.2% to 4.1%, buprenorphine from 5.9% to 7.6%, oxycodone from 0% to 1.8%, tilidine from 1.8% to 2.4%. The most frequently detected opioids in DRD cases were methadone (39.4%) and heroin (20%). Prescription rates between 2011-2017 decreased in Hamburg for nearly all opioids, morphine by - 43.5%, buprenorphine - 43%, codeine - 57%, fentanyl - 25%, tilidine -17%, tramadol - 31%, and hydromorphone -6%. Oxycodone, tapentadol, and piritramide prescription rates increased. For Germany, a decrease in the prescription rates for fentanyl was also found during this period (-12.9 %), although not as pronounced as in Hamburg. Prescription rates for methadone were three to greater than five times higher in Hamburg as compared to the German average due to the higher number of substituted persons per inhabitant. Conclusion: Despite the global problem of opioid abuse, there are significant regional differences in the nature and extent of opioid abuse. It is necessary to collect data at the national level to develop appropriate prevention strategies.

Drug checking: a potential solution to the opioid overdose epidemic?

BACKGROUND: North America is experiencing an overdose epidemic driven in part by the proliferation of illicitly-manufactured fentanyl and related analogues. In response, communities are scaling up novel overdose prevention interventions. Included are drug checking technologies. MAIN BODY: Drug checking technologies aim to identify the contents of illicit drugs. These technologies vary considerably in terms of cost, accuracy, and usability, and while efforts are now underway to implement drug checking programs for people who inject drugs, there remains a lack of rigorous evaluation of their impacts. CONCLUSION: Given the ongoing overdose crisis and the urgent need for effective responses, research on drug checking should be prioritized. However, while such research should be supported, it should be completed before these technologies are widely implemented.

Analytical methodology and assessment of potential second-hand exposure to fentanyl in the hospital surgical setting.

Second-hand exposure to aerosols containing fentanyl and other opiates during surgical procedures has been implicated as possibly contributing to maintenance of addiction among medical professionals, specifically anesthesiologists. This article outlines a pilot study that was conducted to verify a reported finding fentanyl in the air of operating suites. Environmental fentanyl air sampling and analysis methods were developed and evaluated for this study. Multiple sampling media and extraction solvents were evaluated for trace fentanyl air sampling. Non-specific binding losses were reduced by using silanized binder-free glass fiber sampling media with subsequent methanol extraction. Filtration air samples were then collected in surgical suites during the entire operation time from two cardiovascular surgical procedures. Both surgical procedures were conducted at the same hospital but on different days. Samples were extracted and analyzed by high-performance liquid chromatography/tandem mass spectrometry using a capillary high-performance liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer. The total air volume collected per surgery was 290 to 300 L at a rate of 1 LPM giving an limit of quantification for fentanyl of 57 pg/m(3) air (17 pg/filter). No fentanyl was detected in the air during cardiovascular surgical operations from either surgical suite.

Deaths with transdermal fentanyl patches.

Fentanyl is a potent Schedule II narcotic analgesic recommended for use in the management of unremitting pain not controlled by morphine or other opiate/opioid drugs. The danger inherent to fentanyl is its potency (greater than 50-100 times that of morphine) and rapidity of action, causing respiratory depression within minutes of administration. Advisories have been issued on a state and national level to health care providers and through manufacturers' package inserts for patients. Still, as will be demonstrated in this case review, the use of only a single transdermal patch taken as prescribed for the first time can prove fatal. A drug that requires such extensive warnings-that if unheeded lead to death because of its narrow therapeutic/toxic window, should have strict criteria and limited outpatient use. Initial medical observation and documentation for determining tolerance might be required before issuing a prescription. There has been a rise in the popularity of this drug evidenced by increased deaths among drug abusers and more prescriptions written. In the year 2006, the Center for Forensic Sciences in Onondaga County had 8 cases where fentanyl was considered the cause of death, often with other drugs detected in therapeutic concentrations. This number was a marked increase from the 1 to 2 cases occurring annually from 2002 to 2005. All of these 2006 overdoses because of fentanyl involved the transdermal formulation. The investigative data, blood and liver fentanyl levels, and autopsy findings will be presented.