Bedside urine testing for fentanyl in self-reported heroin users in a tertiary Brisbane emergency department.

OBJECTIVE: To determine if patients presenting to our toxicology unit following self-reported heroin use had positive urine immunoassay testing for fentanyl or its analogues. METHODS: Urine samples from consenting patients were tested at the bedside for the presence of opiates or fentanyl and its analogues. RESULTS: Over a 30-month period, 58 patients were recruited. All samples tested positive for opiates, but none tested positive for fentanyl or its analogues. CONCLUSION: In patients presenting to our toxicology unit in Brisbane, we did not find any cases where the urine of patients self-reporting heroin exposure tested positive for fentanyl or its analogues.

Untargeted Metabolomics in Forensic Toxicology: A New Approach for the Detection of Fentanyl Intake in Urine Samples.

The misuse of fentanyl, and novel synthetic opioids (NSO) in general, has become a public health emergency, especially in the United States. The detection of NSO is often challenged by the limited diagnostic time frame allowed by urine sampling and the wide range of chemically modified analogues, continuously introduced to the recreational drug market. In this study, an untargeted metabolomics approach was developed to obtain a comprehensive "fingerprint" of any anomalous and specific metabolic pattern potentially related to fentanyl exposure. In recent years, in vitro models of drug metabolism have emerged as important tools to overcome the limited access to positive urine samples and uncertainties related to the substances actually taken, the possible combined drug intake, and the ingested dose. In this study, an in vivo experiment was designed by incubating HepG2 cell lines with either fentanyl or common drugs of abuse, creating a cohort of 96 samples. These samples, together with 81 urine samples including negative controls and positive samples obtained from recent users of either fentanyl or "traditional" drugs, were subjected to untargeted analysis using both UHPLC reverse phase and HILIC chromatography combined with QTOF mass spectrometry. Data independent acquisition was performed by SWATH in order to obtain a comprehensive profile of the urinary metabolome. After extensive processing, the resulting datasets were initially subjected to unsupervised exploration by principal component analysis (PCA), yielding clear separation of the fentanyl positive samples with respect to both controls and samples positive to other drugs. The urine datasets were then systematically investigated by supervised classification models based on soft independent modeling by class analogy (SIMCA) algorithms, with the end goal of identifying fentanyl users. A final single-class SIMCA model based on an RP dataset and five PCs yielded 96% sensitivity and 74% specificity. The distinguishable metabolic patterns produced by fentanyl in comparison to other opioids opens up new perspectives in the interpretation of the biological activity of fentanyl.

Effect of positive urine fentanyl screen on attitudes toward heroin use.

BACKGROUND: It is unknown if targeted risk reduction counseling in the health care setting, after documented exposure to fentanyl, can affect behavior change to reduce risks and increase utilization of evidence-based overdose prevention strategies. METHODS: We conducted a retrospective analysis of results (7/2018-6/2019) from questionnaire-facilitated counseling by recovery coaches in the emergency department (ED) and primary care settings following disclosure of a urine toxicology positive for fentanyl. RESULTS: Seventy-five percent of N = 101 respondents were neither aware of nor expecting fentanyl in their substances of use. Fifty-three (70 %) of those initially unaware answered that learning about exposure to and the risks from fentanyl changed their thoughts about reducing or abstaining from use. A greater proportion of patients seen in the ED expressed desire to stop or reduce opioid use as compared to ambulatory clinic patients (91 % vs. 46 %, p < 0.001). Of those not already engaged in treatment, 18 % and 15 % were interested in medication and behavioural health treatment, respectively, and each of them indicated a change in thought based on the counseling. Forty-five percent of individuals not yet receiving naloxone endorsed interest in receiving it, and 22 % of all respondents were somewhat or very interested in access to safe consumption sites. CONCLUSION: This study suggests a novel clinical utility in toxicology screens to inform behavior in the setting of illicit fentanyl exposure. In addition to linkages to evidence-based treatment, linkages to harm-mitigating strategies associated with ongoing substance use may be critical to a comprehensive overdose prevention strategy in the clinical setting.

Naloxone-Induced Withdrawal in Individuals With and Without Fentanyl-Positive Urine Samples.

BACKGROUND AND OBJECTIVE: This retrospective analysis of data from heroin users screening for clinical research, sought to determine if more naloxone is needed to precipitate opioid withdrawal among those who regularly use heroin with fentanyl, as opposed to those who use heroin without fentanyl. METHODS: Over the course of three to five screening visits, participants completed assessments of drug use, along with urine toxicology tests at each visit. To test for opioid dependence, 29 participants completed a modified Wang test (score: 0-150) during which an intramuscular dose of naloxone (0.2-0.4 mg) was administered and the severity of withdrawal was quantified. RESULTS: The severity of opioid withdrawal was compared between individuals whose urine toxicology regularly tested positive for fentanyl (N = 15), and those only positive for other opioids (N = 14). No significant differences were found in demographic or drug use between the fentanyl-positive (mean: age 41.1 years, 9.1 bags heroin/d) and fentanyl-negative (42.0 years, 10.0 bags heroin/d) groups. Intramuscular naloxone-precipitated robust withdrawal in both samples (P < .01) with no significant difference (P = .8) in the severity (fentanyl positive [100.6 ± 13.4]; fentanyl negative [82.7 ± 9.6]). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These data suggest that a standard naloxone dose can be equally effective at precipitating withdrawal in individuals using heroin with fentanyl compared to heroin without fentanyl. These data contribute to our understanding of how naloxone antagonizes the effects of fentanyl and may have significant implications for the clinical laboratory and opioid overdose. A prospective clinical laboratory study with the proper opioid maintenance controls is needed to provide a more definitive finding. (Am J Addict 2019;00:00-00).

Street fentanyl use: Experiences, preferences, and concordance between self-reports and urine toxicology.

BACKGROUND: Conducted in Dayton, Ohio, the study aims to characterize user knowledge and experiences with non-pharmaceutical fentanyl-type drugs (NPFs) and compare self-reports with urine toxicology for NPFs and heroin. METHODS: Between May 2017-January 2018, 60 individuals who self-reported heroin/NPF use were interviewed using structured questionnaire on socio-demographics, NPF and other drug use practices. Unobserved urine samples were collected and analyzed using: 1) liquid-chromatography-tandem mass spectrometry (LC-MS/MS)-based method (Toxicology lab) to identify 34 fentanyl analogues, metabolites, and other synthetic opioids; 2) immunoassay-based method to screen for opiates (heroin). Sensitivity, specificity and Cohen's kappa were calculated to assess agreement between self-reports and urine toxicology. RESULTS: The sample was 52% female, and over 90% white. Almost 60% reported preference for heroin, and 40% for NPF. Participants endorsed a number of ways of distinguishing heroin from NPF, including appearance (88.3%), effects (76.7%), taste (55%), and information provided by dealers (53.3%). Almost 80% felt confident they could distinguish heroin from NPF, but knowledge about fentanyl analogues was limited. LC-MS/MS testing identified 8 types of NPFs. Over 88% tested positive for NPFs, including 86% fentanyl, 48% carfentanil, 42% acetyl fentanyl. About 47% screened positive for opiates/heroin, and all of them were also positive for NPFs. When comparing self-reported use of NPF to urine toxicology, sensitivity and specificity were relatively high (84% and 83.3%, accordingly), while Cohen's Kappa was 0.445, indicating fair agreement. Sensitivity and specificity were lower for heroin (77.8% and 50.0%, accordingly), and Cohen's Kappa was 0.296, indicating low agreement between self-reports of heroin use and urine toxicology. DISCUSSION: Nearly 90% of the study participants tested positive for NPF-type drugs. Participants were more likely to over-report heroin use and underreport NPF use. The majority had little knowledge about fentanyl analogues. Study findings will inform development of novel harm reduction approaches to reduce overdose mortality.

Analysis of Acetyl Fentanyl in Postmortem Specimens by Gas Chromatography-Mass Spectrometry (GC-MS): Method Validation and Case Report.

In 2013, the Centers for Disease Control and Prevention released a warning regarding a new recreational drug, acetyl fentanyl. Acetyl fentanyl is a µ-opioid receptor agonist, and its pharmacological effects include euphoria, altered mood, miosis and central nervous system depression. The objective of this report was to develop a sensitive and specific method for the quantitation of acetyl fentanyl by gas chromatography-mass spectrometry in postmortem casework. Acetyl fentanyl was isolated from biological matrices using solid-phase extraction and acetyl fentanyl-13C6 was employed as an internal standard. The method was validated utilizing the Scientific Working Group for Forensic Toxicology's published method validation parameters, and the biological matrices used for analysis were postmortem blood and urine. In addition to the quantitation of acetyl fentanyl, a demographic study of cases obtained from the Rhode Island Office of State Medical Examiners and the University of Florida Health Pathology Laboratories-Forensic Toxicology Laboratory was performed to examine potential risk factors for acetyl fentanyl use. The results from this study found that the blood concentrations in these individuals ranged from 17 to 945 ng/mL. This suggests acetyl fentanyl is less potent than its prototype drug, fentanyl and requires an increased dose to achieve its desired effects. The demographic analysis indicated white males aged 21-40 years and individuals with a previous history of drug use have the highest risk for acetyl fentanyl abuse.

A Fatality Involving Furanylfentanyl and MMMP, with Presumptive Identification of Three MMMP Metabolites in Urine.

The prevalence of new psychoactive substances (NPS) on the illicit drug market continues to grow, with new analogs being routinely synthesized. Routes of administration for these compounds are also diversifying, and recent research has shown an increase in the incorporation of NPS into vaping liquids. Among the most commonly encountered NPS are the cathinone and fentanyl analogs. Fentanyl analogs in particular have been implicated in a significant number of deaths, usually in combination with other prescription and illicit drugs. We report the case of a 44-year-old male with a history of polysubstance abuse found deceased at his home address. Items located within the vicinity of the deceased were found to contain furanylfentanyl and 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MMMP also known as MTMP, MMTMP, Irgacure 907 and Caccure 907). Both of these compounds were detected in the post-mortem peripheral blood of the deceased: furanylfentanyl at 1.6 ng/mL and MMMP at 6.7 ng/mL. MMMP is an unrestricted, commercially available photo-initiator used in the printing and polymer industry, which structurally can be classed as a highly modified cathinone. Although MMMP has been found previously in drug seizures, this is the first fatality in which MMMP has been detected. A number of other prescription and illicit drugs were also detected in the blood. MMMP was not detected in the post-mortem urine; however three metabolites, beta-hydroxy-MMMP, beta-hydroxy-MMMP-sulfoxide and beta-hydroxy-MMMP-sulfone, were presumptively identified. The significance of MMMP to the cause of death is uncertain as its pharmacological and toxicological profile is unclear.

Fentanyl exposure among patients seeking opioid treatment.

AIM: Overdoses attributed to the potent opioid agonist fentanyl have substantially increased in recent years. Despite these serious public health consequences, many opioid treatment providers do not currently include a fentanyl assay in their urine toxicology testing. As a result, extent of fentanyl exposure and related risks among individuals with opioid use disorder often remains unknown. We examined the prevalence of fentanyl exposure among patients seeking or enrolled in opioid agonist treatment. METHODS: Six hundred urine specimens were collected from adults entering (n = 100) or enrolled in (n = 500) opioid agonist treatment and analyzed using the clinic's standard opioid panel, supplemented with a 100 ng/ml fentanyl assay. RESULTS: Of the 100 specimens collected from patients at treatment intake, 19 (19%) tested positive for fentanyl. Importantly, 17 (90%) of those fentanyl-positive specimens were also positive for heroin. Of the 500 collected from patients in treatment, 17 (3%) of specimens tested positive for fentanyl. Of those, 11 (92%) were also positive for heroin. CONCLUSION: These data illustrate a concerning degree of fentanyl exposure among patients seeking treatment and suggest that much of this exposure may have stemmed from fentanyl-containing heroin. Given the unprecedented recent surges in fentanyl-related overdoses, efforts to identify fentanyl exposure are critical. In particular, the point of treatment entry permits a rare systematic opportunity for medical and clinical staff to address fentanyl use and risks with incoming patients.

Characteristics of opioid-maintained clients smoking fentanyl patches: The importance of confirmatory drug analysis illustrated by a case series and mini-review.

The increase in opioid prescribing in many European countries over the last decade has raised concerns about associated diversion, overdose, and mortality. Fentanyl is one of these synthetic opioids that is typically prescribed as a transdermal patch for pain that requires continuous pain relief and has been the focus of investigation due to reports of overdose and death. We report a case series of 14 drug addiction treatment entrants, who entered treatment in a service located in the region of Southern Denmark from August 2015 to December 2015 for smoking fentanyl patches. Clients presented with difficulties breathing and pains in the lungs. The clients had a history of past opioid use, including heroin. Relapses resulted in treatment disengagement. Immunoassays for fentanyl were used in the service. In some cases, false negative results occurred. Clients' urine samples were subsequently analysed in a collaborating laboratory. Seven clients tested positive for fentanyl. One client was positive for both fentanyl and heroin. Analyses were also positive for other opioids and metabolites in 6 clients, predominantly codeine and oxycodone. Results from confirmatory analysis contributed to clearer insights into clients' drug histories, which facilitated personalised care plans consisting of opioid agonist therapy informed by confirmed drug use. In Denmark, prescription levels of fentanyl are high, which has been accompanied by observations of diversion and smoking in a smaller population. In addition to revision of inappropriate prescribing to reduce diversion, we recommend increased reliance upon confirmatory drug analysis in the addiction treatment sector in Denmark.

A Novel Oral Fluid Assay (LC-QTOF-MS) for the Detection of Fentanyl and Clandestine Opioids in Oral Fluid After Reported Heroin Overdose.

INTRODUCTION: The adulteration of heroin with non-pharmaceutical fentanyl and other high-potency opioids is one of the factors contributing to striking increases in overdose deaths. To fully understand the magnitude of this problem, accurate detection methods for fentanyl and other novel opioid adulterant exposures are urgently required. The objective of this work was to compare the detection of fentanyl in oral fluid and urine specimens using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) in a population of heroin users presenting to the Emergency Department after overdose. METHODS: This was a prospective observational study of adult Emergency Department patients who presented after a reported heroin overdose requiring naloxone administration. Participants provided paired oral fluid and urine specimens, which were prepared, extracted, and analyzed using a dual LC-QTOF-MS workflow for the identification of traditional and emerging drugs of abuse. Analytical instrumentation included SCIEX TripleTOF® 5600+ and Waters Xevo® G2-S QTOF systems. RESULTS: Thirty participants (N = 30) were enrolled during the study period. Twenty-nine participants had fentanyl detected in their urine, while 27 had fentanyl identified in their oral fluid (overall agreement 93.3%, positive percent agreement 93.1%). Cohen's Kappa (k) was calculated and demonstrated moderately, significant agreement (k = 0.47; p value 0.002) in fentanyl detection between oral fluid and urine using this LC-QTOF-MS methodology. Additional novel opioids and metabolites, including norfentanyl, acetylfentanyl, and U-47700, were detected during this study. CONCLUSION: In this study of individuals presenting to the ED after reported heroin overdose, a strikingly high proportion had a detectable fentanyl exposure. Using LC-QTOF-MS, the agreement between paired oral fluid and urine testing for fentanyl detection indicates a role for oral fluid testing in surveillance for nonpharmaceutical fentanyl. Additionally, the use of LC-QTOF-MS allowed for the detection of other clandestine opioids (acetylfentanyl and U-47700) in oral fluid.

Identification and physicochemical characterization of 4-fluorobutyrfentanyl (1-((4-fluorophenyl)(1-phenethylpiperidin-4-yl)amino)butan-1-one, 4-FBF) in seized materials and post-mortem biological samples.

During the last decade, a substantial growth in new psychoactive substances (NPS) has been recorded. Within this group, a considerably fast-growing sub-group is represented by the opioids, which are based on modifications of the fentanyl structure. In this study, identification and analytical characterization of a new fentanyl derivative, 4-fluorobutyrfentanyl (1-((4-fluorophenyl)(1-phenethylpiperidin-4-yl)amino)butan-1-one, 4-FBF), is described. Apart from the seized powder, 4-FBF was also identified in the e-cigarette liquid secured in Case 1. The concentration of the compound in the liquid was 35 mg/mL. The main component of the liquid was glycerol, and nicotine was also present. This substance was detected in seized material that originated from the illegal drug market in Poland. To the best of the authors' knowledge, this report presents the first two analytically confirmed cases of fatal intoxication associated with 4-FBF. Case 1 was a 26-year-old male drug user who was found dead at home. Case 2 was a 25-year-old female, occasional user of NPS and drugs, who was also found dead at home. The concentrations of 4-FBF in blood were 91 and 112 ng/mL and in urine 200 and 414 ng/mL. The concentrations of 4-FBF in liver and kidney were 902 and 411 ng/g, and 136 and 197 ng/g, for Case 1 and Case 2, respectively. Copyright © 2016 John Wiley & Sons, Ltd.

Fentanyl transdermal absorption linked to pharmacokinetic characteristics in patients undergoing palliative care.

Delivery rates and plasma concentrations vary among patients treated with fentanyl patches. Absorption and urinary excretion characteristics of fentanyl were studied in patients undergoing palliative care. Almost 500 patches were analyzed for residual fentanyl content. Fentanyl and norfentanyl levels were determined in the urine of 50 patients. General and mixed effects linear regression models were established for the relationship between fentanyl dose rate and urinary excretion and to incorporate influencing factors. For different patch nominal dose strengths, wide but comparable variability in estimated dose rate and delivery efficiency was observed (coefficients of variation of 15% to 17%). Fentanyl delivery efficiency was 8.5% higher for patches of 25 microg/h as compared to 75 microg/h and, accordingly, 7.5% for patch application on the arm as compared to the leg. Urinary fentanyl and norfentanyl concentrations varied considerably. The general linear model revealed a positive effect of the calculated transdermal dose rate on urinary fentanyl levels, explaining 34% of the variability (P < .0001). In addition, gender (P = .04) and type of cancer pathology (P = .03) exerted significant effects on the linear model, explaining 40% and 64% of the variability, respectively. Delivery efficiency of fentanyl patches can vary substantially, possibly leading to either underdosing or overdosing.

Quantitation of fentanyl in blood and urine using gas chromatography-mass spectrometry (GC-MS).

Fentanyl is a potent, short-acting synthetic opioid analgesic. Fentanyl is measured in blood and urine following mixed-mode solid phase extraction. The specimens are fortified with deuterated internal standard and a five-point calibration curve is constructed. The final extracts are reconstituted in methanol and analyzed using selected ion monitoring gas chromatography-mass spectrometry.

Determination of fentanyl in human plasma and fentanyl and norfentanyl in human urine using LC-MS/MS.

Fentanyl, a potent analgesic drug, has traditionally been used intravenously in surgical or diagnostic operations. Formulations with fentanyl in oral transmucosal delivery system and in transdermal depot-patch have also been developed against breakthrough pain in cancer patients. In this report, LC-MS/MS methods to determine fentanyl in human plasma as well as fentanyl and its main metabolite, norfentanyl, in human urine are presented together with validation data. The validation ranges were 0.020-10.0 and 0.100-50.0 ng/ml for fentanyl in plasma and urine, respectively, and 0.102-153 ng/ml for norfentanyl in urine. Liquid-liquid extraction of the compounds fentanyl, norfentanyl and the deuterated internal standards, fentanyl-d5 and norfentanyl-d5 from the matrixes was applied and separation was performed on a reversed phase YMC Pro C18-column followed by MS/MS detection with electrospray in positive mode. The inter-assay precision (CV%) was better than 4.8% for fentanyl in plasma and 6.2% and 4.7% for fentanyl and norfentanyl, respectively, in urine. The ruggedness of the methods, selectivity, recovery, effect of dilution and long-term stability of the analytes in plasma and urine were investigated. Effect of haemolysis and stability of fentanyl in blood samples were also studied. The methods have been applied for the determination of fentanyl in plasma samples and fentanyl/norfentanyl in urine samples taken for pharmacokinetic evaluation after a single intra-venous (i.v.) dose of 75 microg fentanyl.

Highly sensitive gas chromatographic-mass spectrometric screening method for the determination of picogram levels of fentanyl, sufentanil and alfentanil and their major metabolites in urine of opioid exposed workers.

Highly sensitive and specific analytical GC-MS procedures were developed and comprehensively validated for the determination of the opioid narcotics fentanyl, sufentanil and alfentanil and their major nor-metabolites in urine of potentially exposed opioid production workers. A simple, one step extraction protocol was developed using commercially available solid phase extraction (SPE) columns to recover all analytes from urine. The secondary amine functionalities of the nor-metabolites were derivatized to form stable, pentafluorobenzamide (PFBA)-derivatives with good chromatographic properties. Using the penta-deuterated analogues as internal standards, a limit-of-detection (LOD) of 2.5 pg fentanyl/ml, 2.5 pg sufentanil/ml and 7.5 pg alfentanil/ml urine was achieved. For the opioid metabolites the LODs were found to be <50 pg/ml urine. The developed analytical procedures show excellent intra-assay accuracy, particularly considering the ultra low levels of the analytes, with relative errors generally below 10%. Overall, an excellent reproducibility was observed with coefficients of variation below 10% at all spike levels for all opioid parent compounds and their metabolites, except for low norfentanyl concentrations. Upon storage at -30 degrees C urine samples were found to be stable for at least 2 months as no significant losses of either compound were observed. The developed analytical procedures have been successfully applied in a biological monitoring survey of fentanyl exposed production workers.

Spinal anesthesia for arthroscopic knee surgery.

BACKGROUND AND OBJECTIVE: The purpose of the study was to compare the effects of adding 50 microg of morphine, 25 microg of fentanyl or saline to 6 mg of hyperbaric bupivacaine on postoperative analgesia and time to urination in patients undergoing arthroscopic knee surgery under spinal anesthesia. METHODS: The study was designed in a prospective, randomized, double-blinded and placebo-controlled manner. Sixty ASA I-II patients were randomized into the following three groups: Group BM: 6 mg of bupivacaine and 50 microg of morphine, Group BF: 6 mg of bupivacaine and 25 microg of fentanyl, and Group BS: 6 mg of bupivacaine and saline. Selective spinal anesthesia was performed in a lateral decubitus position, with the operative knee dependent for 10 min. RESULTS: In all groups satisfactory anesthesia was provided during the operation. There was a statistically significant difference between all the groups in times to voiding [Group BM 422 +/- 161 min; Group BF 244 +/- 163 min; Group BS 183 +/- 54 min (mean +/- SD)]. The incidence of pruritus was significantly greater in Group BM (80%) and BF (65%) in comparison with Group BS (no pruritus) (P < 0.05). The incidence of nausea was significantly increased in Group BM (35%) in comparison with Group BF (10%) and Group BS (P < 0.05). Analgesic consumption was significantly greater in Group BS in comparison with Groups BM and BF (P < 0.01). CONCLUSIONS: We conclude that during spinal anesthesia even mini-dose intrathecal morphine is not acceptable for outpatient surgery due to side-effects, especially severely prolonged time to urination.

Development of a gas chromatographic-mass spectrometric drug screening method for the N-dealkylated metabolites of fentanyl, sufentanil, and alfentanil.

A sensitive, specific urinary assay for fentanyl, sufentanil, and alfentanil based on their N-dealkylated metabolites is described. Norfentanyl, norsufentanil-noralfentanil, and 2H5-norfentanyl are synthesized and characterized by standard analytical techniques. Derivatization of these secondary amines to yield the pentafluorobenzamides produces stable products with good gas chromatographic properties and unique, high-mass fragments in their mass spectra. These properties are utilized to develop a drug screening procedure based on gas chromatography-mass spectrometry to detect these major metabolites in human urine. The metabolites are isolated from urine samples by a liquid-liquid extraction procedure. The method allows for detection of metabolite concentrations as low as 0.3 ng/mL.

Fatal fentanyl intoxication following excessive transdermal application.

The case history and toxicological findings of a fatal fentanyl intoxication due to the application of multiple transdermal patches are presented. An 83 year-old white female with terminal cancer was found dead with three 100 mg/h fentanyl patches on her chest. The autopsy and subsequent histological studies revealed extensive areas of gastric carcinoma, a large atrial tumor, ulceration of esophagus, metastasis of peripancreatic lymph nodes and a recent surgical removal of part of the lower lobe of the left lung. Toxicological analysis by GC/MS yielded fentanyl concentrations of blood, 25 ng/mL; brain, 54 ng/g; heart 94 ng/g; kidney 69 ng/g; and liver 104 ng/g. The cause of death was determined to be fentanyl overdose and the manner of death was ruled undetermined as the investigation was unable to conclusively establish whether this was an accidental overdose, a suicide, an assisted suicide, or possible a homicide. This case demonstrates the need for caution in self-administration of transdermal fentanyl patches, in particular, the dangers inherent in the application of multiple patches which can result in the release of potentially toxic or lethal doses.

Gas chromatographic-mass spectrometry and gas chromatographic-Fourier transform infrared spectroscopy assay for the simultaneous identification of fentanyl metabolites.

Fentanyl, a synthetic opioid, undergoes important biotransformation to several metabolites. A gas chromatographic-mass spectrometric assay was applied for the simultaneous analysis of fentanyl and its major metabolites in biological samples. The identification of different metabolites was performed by gas chromatography-mass spectrometry (electronic impact and chemical ionisation modes) and gas chromatography-Fourier transform infrared spectroscopy. In the present study, rat and human microsomes incubation mixtures and human urines were analysed. In vitro formation of already known fentanyl metabolites was confirmed. The presence of metabolites not previously detected in human urine is described.

Measurements of fentanyl and sufentanil in blood and urine after surgical application. Implication in detection of abuse.

An increase in cases of death from overdose and abuse from fentanyl or sufentanil is being encountered by the Bexar County Forensic Science Center in San Antonio, Texas. These drugs have been abused almost solely by health care professionals. The fentanyl derivatives cannot currently be detected by routine laboratory drug-screening programs. Forensic toxicology assays that identify the specific analyte must be used. We report a sensitive assay for detection of fentanyl and sufentanil with a detection limit of -0.5 ng/ml. In addition, results from the analysis of urine and blood samples obtained up to 72 h after drug administration to five patients undergoing cardiac bypass surgery who had received either fentanyl or sufentanil are described. The new procedure enables detection of these drugs more readily, in smaller amounts, and for a longer period of time after use than previously possible. We hope this will lead to intervention and treatment in those abusing the drugs.