Determination Of Fentanyl Research Articles

Semi-automated filter micro-solid phase extraction based on urea-formaldehyde microsphere followed by corona discharge-ion mobility spectrometry for simultaneous detection of fentanyl and nor-fentanyl in urine

In this work, semi-automated filter micro-solid phase extraction (SA-FμSPE) packed by urea–formaldehyde (UF) microspheres coupled with corona discharge ionization-ion mobility spectrometry (CD-IMS) was developed for the extraction and determination of fentanyl and nor-fentanyl in urine samples. UF microspheres, synthesized by aqueous polymerization, can be used to achieve effective extraction of analytes through multiple adsorption interactions such as hydrophobic, dipole–dipole and hydrogen bonding interactions. UF microspheres dispersed in methanol were packed in the filter by syringe, and the extraction process was performed by a portable automatic filter extraction device. The parameters affecting extraction efficiency (i.e., extraction time, the flow rate of extraction, pH value, amount of sorbent, ionic strength, cycle times of desorption, and type of eluent) were investigated. Then, the eluate containing fentanyl and nor-fentanyl was simultaneously analyzed by CD-IMS in positive mode. Under the optimal extraction conditions, the detection limits for the target compounds were 5.00 ng mL−1 and 8.00 ng mL−1, respectively. The spiked recoveries were in the range of 81.97 % −112.37 % by testing the real samples and validated by UHPLC-MS. Thus, the satisfactory results reveal that SA-FμSPE coupled with CD-IMS has great potential for on-site extraction and detection of fentanyl and nor-fentanyl in urine samples.

Determination of fentanyl and acetylfentanyl in soil in their intact form and orthogonal corroboration of their presence by EI-GC-MS using chloroformate chemistry

In the field of forensic chemistry, methods for identifying and characterizing illicit drugs remain of great interest to government and law enforcement entities. To this end, the unambiguous identification of a drug in the environment (e.g., soil) prompts further investigation into the possibility of a clandestine point of production for such drug. In this report, a method for the analysis of the two common synthetic opioids fentanyl and acetylfentanyl in a soil matrix when present separately at 1 and 10 μg/g by electron ionization gas chromatography-mass spectrometry (EI-GC-MS) is presented. The method involves the initial extraction of the intact opioids followed by their reaction with 2,2,2-trichloroethoxycarbonyl chloride (Troc-Cl) to predictably generate Troc-modified norfentanyl, Troc-noracetylfentanyl and 2-phenylethyl chloride products that can be used to retrospectively corroborate the identity of the opioid by EI-GC-MS. Estimated method detection limits (MDLs) for the Troc-norfentanyl and Troc-noracetylfentanyl species were 15.4 and 13.6 ng/mL respectively from the soil matrix extracts employed (Virginia type A soil) while the calculated method’s LOQ values were 45.7 and 40.4 ng/mL respectively. The protocol presented herein describes for the first time the analysis of these highly toxic and common synthetic opioids in a soil matrix as well as their retrospective confirmation by analyzing the products arising from their reaction with Troc-Cl by EI-GC-MS.

The Development of a Multisensory Stripping Voltammetry Method for the Analysis of Medical Preparations: Determination of Fentanyl in Lacrimal Fluid

The Development of a Multisensory Stripping Voltammetry Method for the Analysis of Medical Preparations: Determination of Fentanyl in Lacrimal Fluid

Determination of Fentanyl, Alpha-Methylfentanyl, Beta-Hydroxyfentanyl and the Metabolite Norfentanyl in Rat Urine by LC-MS-MS.

Fentanyl and its analogs are potent synthetic opioids with a high potential for abuse and dependence. They have become major contributors to opioid deaths. This study aimed to determine whether the metabolites of fentanyl, alpha-methylfentanyl and beta-hydroxyfentanyl, excreted in the urine, can demonstrate historical drug exposure. Fentanyl is primarily metabolized via CYP3A4 into norfentanyl, although there is little research on its metabolization into alpha-methylfentanyl and beta-hydroxyfentanyl. We conducted in vitro experiments with human liver microsomes (HLMs) and rat liver microsomes (RLMs) to elucidate the major metabolic pathways of alpha-methylfentanyl and beta-hydroxyfentanyl using ultra-high-performance liquid chromatography coupled with mass spectrometry. The results showed that both alpha-methylfentanyl and beta-hydroxyfentanyl were predominantly metabolized into norfentanyl in HLM and RLM. Urine samples were collected at different intervals from 0 h to 72 h after intravenous administration of alpha-methylfentanyl and beta-hydroxyfentanyl (20 μg/kg) to Sprague-Dawley rats. We prepared the samples by liquid-liquid extraction, and the internal standard (IS) was cariprazine. A sensitive, rapid liquid chromatography-tandem mass spectrometry method was developed and validated to determine four analytes in the urine. The lower limit of qualification in urine was 2 pg/mL for fentanyl, 5 pg/mL for alpha-methylfentanyl, 10 pg/mL for beta-hydroxyfentanyl and 40 pg/mL for norfentanyl. The analytical range was 0.002-2 ng/mL for fentanyl, 0.005-5 ng/mL for alpha-methylfentanyl, 0.01-10 ng/mL for beta-hydroxyfentanyl and 0.04-40 ng/mL for norfentanyl. All analytes demonstrated good linearity (R2 > 0.99). The extraction recoveries were in the 67.8%-92.1% range, and the IS-normalized matrix effects were between 55.5% and 74.0% (coefficient of variance < 15%). Our data indicated that norfentanyl has a higher concentration in rat urine and was detectable for at least 3days after exposure to these compounds. This developed method may be useful in various fields, including forensic analysis, workplace drug testing and monitoring drug abuse.

Rapid screening and determination of fentanyl and its analogues in drugs by liquid chromatography- quadrupole time-of-flight mass spectrometry

A method based on liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was developed for the simultaneous screening and determination of fentanyl and its 26 analogs in liquid and solid powder drugs. The established method involves successive extraction by 5 mL 75% (v/v) acetonitrile aqueous solution and 5 mL acetonitrile, followed by clean-up using the hydrophilic lipophilic balance (HLB) solid-phase extraction method. Detection was achieved by electrospray ionization (ESI) in the positive mode, TOF-MS, and information-dependent acquisition (IDA)-MS/MS acquisition; the external standard method was adopted for quantification. Two databases of accurate mass and fragment ions were created. The standard matrix-matched calibration curves of the 27 target compounds were linear in the range of 5.00-100 μg/L, with the correlation coefficients (r2)>0. 99. The limits of quantification for the 27 target compounds were 10.0 μg/kg. The recoveries for all the target compounds in vitamin C tablet, headache powder, cough syrup, and transdermal patch samples were in the ranges of 82.9%-106%, 84.8%-106%, 86.9%-109%, and 83.1%-106%, respectively, with relative standard deviations ranging from 0.38% to 8.71% (n=6). The results demonstrated that the developed method is rapid and sensitive for the simultaneous monitoring and determination of fentanyl and 26 its analogs in liquid and solid powder drugs.

Determination of fentanyl and 19 derivatives in hair: Application to an Italian population

Nowadays fentanyl and its analogs represent the most numerous group among synthetic opioid and, due to their higher potency in comparison to traditionl opioids, the main cause of the critical increase of fatal intoxications opioids-intake related in the USA. We developed an LC-MS/MS method for the detection and quantification of fentanyl and its analogs in hair, then applied to 117 real samples, 97 collected from drugs users and 20 from postmortem cases of drugs addicts. The ionization and MRM parameters have been optimized for 27 molecules: 20 reached the acceptance criteria for identification and quantification. LODs and LOQs of 0.2 and 0.5 pg/mg, respectively, were reached for most of the substances, except for five compounds for which were set at 0.5 and 1.0 pg/mg. 2 out of the 97 samples collected from drug users tested positive; one for carfentanil, butyryl fentanyl, THFF and ocfentanil; the other one for 3-methyl norfentanyl. 2 out of the 20 postmortem samples show positive results: one only for fentanyl, the other for furanyl fentanyl, acetyl fentanyl, methoxyacetyl fentanyl, methoxyacetyl norfentanyl, ocfentanil and 4-ANPP. Despite the relatively small number of samples, the results suggest that the method should be included in routine hair analyses for monitoring the new synthetic opioids potential intake by drug users.

Fentanyl related cases. The situation in Greece

Objective: Fentanyl is used as a pre-anesthetic medication and it is also prescribed for the management of chronic pain through the delivery method of transdermal patches. It is used or abused, as a recreational drug, worldwide. As a result, a significant number of fentanyl related deaths have been recorded in many countries, as well as in Greece. The aim of this paper is to present the current situation in Greece through the report of specific fentanyl related cases and to discuss the different aspects of fentanyl abuse. Methods: A gas chromatography-mass spectrometric method was developed, validated and applied for the determination of fentanyl in biological fluids during the investigation of fentanyl related cases. Results: Eight cases, lethal or not, have been recorded the last four years in Greece, where fentanyl blood concentration was found up to 22.7 ng/mL. Five of the cases concerned therapeutic use of fentanyl and three were related to abuse of the drug. Furthermore, six of these cases concerned fentanyl transdermal patches. Conclusions: The commercial success of transdermal fentanyl is impressive and ensures that the drug will remain in market for years to come. The litigation surrounding the use and abuse of fentanyl patches is a major concern today. Warning and information to users and practitioners about the possibility of adverse effects, even death, law enforcement action, prescribing regulations, and availability of rapid and accurate analytical methods for the determination of fentanyl in biological specimens, must be under deliberation.

Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Fentanyl and its Major Metabolite Norfentanyl in Critically Ill Neonates

Fentanyl is a widely used opioid analgesic in the intensive care unit. In critically ill neonates, continuously infused fentanyl is part of the standard treatment regimen for sedation and pain control. Little is known about fentanyl pharmacokinetics in specific clinical indications, as in asphyxiated neonates with therapeutic hypothermia treatment. In this report, we introduce a liquid chromatography-tandem mass spectrometry method (LC-MS/MS-method) to determine concentrations of fentanyl and its major metabolite norfentanyl in critically ill newborns. 100 μl serum samples were precipitated with acetonitrile containing the isotopically labeled internal standard fentanyl-D5. The supernatant was evaporated to dryness and reconstituted with mobile phase. Chromatographic separation was achieved on a C18 column with a gradient flow. LC-MS/MS detection was performed using a triple-stage quadrupole mass spectrometer working in selected reaction monitoring mode with positive electrospray ionization. Linearity was demonstrated over the concentration range of 0.1 to 40 and 39.4 ng/ml for fentanyl and norfentanyl respectively. Inter- and intraday accuracies and precisions were within the acceptance ranges. The lower limit of quantification was 0.02 and 0.09 ng/ml for fentanyl and norfentanyl. The method was successfully applied to newborns with hypoxic-ischemic encephalopathy treated with whole body hypothermia, which allowed accurate determination of fentanyl and norfentanyl concentrations as a basis for pharmacokinetic analysis.

Determination of fentanyl, metabolite and analogs in urine by GC/MS

A rapid and sensitive method for the simultaneous determination of alfentanyl, sufentanyl and fentanyl (and its major metabolite norfentanyl) in urine was developed and validated. The method involved a liquid-liquid extraction in alkaline conditions, derivatization with pentafluoropropionic anhydride to improve the sensitivity for norfentanyl and subsequent analysis in GC/MS. The LODs are 0.08 ng ml(-1) for all substances (0.04 ng ml(-1) for alfentanyl). Intra- and inter-day precision coefficient of variation was always below 15%; mean relative error (accuracy) was always below 15%. The method was linear for all analytes, with quadratic regression of calibration curves always higher than 0.99. The method was applied to real samples of subjects who had received therapeutic doses of fentanyl, showing its suitability for the determination of low levels of these substances. The method was also applied to a subject whose death was attributed to fentanyl overdose.

Determination of fentanyl in human breath by solid-phase microextraction and gas chromatography–mass spectrometry

Fentanyl, a kind of intravenous narcotic analgesic, is widely used in clinical anesthesia. As a potential pollution, it was detected in both the air of the cardiothoracic operating room and patients' expiratory circuit. However, whether the fentanyl in patients' expiratory circuit is exhaled by patients is unknown. In this study, breath samples were taken from the expiratory circuits of anesthetic machine linked to the patients who received intravenous fentanyl, a solid-phase microextraction (SPME) coupled with gas chromatography–mass spectrometry (GC–MS) method was developed to detect and quantify fentanyl in breath samples. The parameters influencing adsorption (extraction time, temperature,) and desorption (desorption time) of the analyte on the fiber were investigated and validated for method development. The developed method was proved to be simple, easy, and inexpensive and offer high sensitivity and reproducibility. Linear range was obtained from 0.05 ng/mL to 0.8 ng/mL. The limit of detection was 0.01 ng/mL while an interday precision of less than 12.13% ( n = 5) could be achieved. Six patients were involved in this study; results showed presence of fentanyl in the breath of patients who received intravenous fentanyl, and fentanyl concentrations in breath varied from 6.00 to 20.89 pg/mL. In conclusion, fentanyl can be exhaled by patients who received intravenous fentanyl.

Determination of fentanyl in biological and water samples using single-drop liquid–liquid–liquid microextraction coupled with high-performance liquid chromatography

A single-drop liquid–liquid–liquid microextraction (LLLME) method coupled with high-performance liquid chromatography (HPLC) was developed for the determination of fentanyl in biological (plasma and urine) and wastewater samples. Fentanyl is a potent synthetic narcotic analgesic administered in the form of a transdermal patch for the management of chronic pain. Fentanyl was extracted from 0.01 M NaOH solution (donor phase) into a thin layer of organic phase (100 μL), then back-extracted into 5 μL of the acidic acceptor microdrop (1 × 10 −3 M HClO 4) immersed in the organic membrane from the tip of a 25-μL HPLC syringe. After the extraction, the microdrop was withdrawn into the syringe and injected directly into a HPLC system for analysis. The parameters influencing the extraction efficiency including the organic solvent and its volume, acceptor microdrop volume, composition of the donor and acceptor phases, stirring rate, temperature, salt addition and pre- and back-extraction times were investigated and optimized. At the most appropriate conditions (100 μL of n-octane, 3.6 mL of the donor phase maintained at 0.01 M NaOH, 5 μL of 1 × 10 −3 M HClO 4 as the acceptor microdrop, stirring rate of 1000 rpm for pre-extraction and 700 rpm for back-extraction, 30 °C, no salt addition, 30 min for pre-extraction and 20 min for back-extraction), an enrichment factor (EF) of 355 was obtained. The limit of detection (LOD) was 0.1 ng mL −1 (based on S/N = 3) and intra- and inter-day relative standard deviations less than 9% were obtained. The calibration graph was linear within the range of 0.5–1000 ng mL −1 with the correlation coefficient ( r) of 0.9999. Finally, the feasibility of the proposed method was evaluated by extraction and determination of fentanyl in plasma, urine and wastewater samples and satisfactory results were obtained.

Determination of Fentanyl in Sweat and Hair of a Patient using Transdermal Patches

Fentanyl is a synthetic opioid used to treat intense chronic pain. In this study, the authors report detection and quantification of fentanyl in sweat and hair of a patient receiving fentanyl (25 microg/h) via a transdermal therapeutic system (TTS) for 22 days. Sweat was collected using sweat patches every night on days 13-21 of the therapy, and hair was collected 12 weeks after the end of the treatment. Detection and quantification was performed with liquid chromatography-tandem mass spectrometry using electron spray ionization in selected reaction monitoring mode. Alfentanyl was used as internal standard for quantification in hair and in sweat. Sodium ions have been used as endogenous internal reference for determination of volume of sweat excreted on each patch. Results show presence of fentanyl in both matrices. Fentanyl concentrations in sweat varied from 0.17 to 1.02 ng/microL, and time-resolved segmented hair analysis showed a maximum fentanyl concentration of 0.48 ng/mg of hair during the period of the therapy.

Analysis of pain management drugs, specifically fentanyl, in hair: Application to forensic specimens

This article discusses the immunoassay screening of pain management drugs, and the mass spectrometric confirmation of fentanyl in human hair. Hair specimens were screened for fentanyl, opiates (including oxycodone), tramadol, propoxyphene, carisoprodol, methadone, and benzodiazepines and any positive results were confirmed using gas chromatography or liquid chromatography with mass spectral detection. The specific focus of the work was the determination of fentanyl in hair, since autopsy specimens were also available for comparison with hair concentrations. Using two-dimensional gas chromatography with electron impact mass spectrometric detection, fentanyl was confirmed in four of nine hair specimens collected at autopsy. The accuracy of the assay at 10 pg/mg was 95.17% and the inter-day and intra-day precision was 5.04 and 13.24%, respectively ( n = 5). The assay was linear over the range 5–200 pg/mg with a correlation of r 2 > 0.99. The equation of the calibration curve forced through the origin was y = 0.0053 x and the limit of quantitation of the assay was 5 pg/mg. The fentanyl concentrations detected were 12, 17, 490, and 1930 pg/mg and the results were compared with toxicology from routine post-mortem analysis. The screening of pain management drugs in hair is useful in cases where other matrices may not be available, and in routine testing of hair for abused drugs.

SIMULTANEOUS DETERMINATION OF FENTANYL AND MIDAZOLAM IN PLASMA USING DIRECT SOLID-PHASE MICROEXTRACTION BEFORE GAS CHROMATOGRAPHY–MASS SPECTROMETRY ANALYSIS

ABSTRACT We developed a rapid, specific, and sensitive solid-phase extraction method followed by gas chromatography–mass spectrometry analysis for the determination of fentanyl, midazolam or both drugs simultaneously in plasma samples. Various solid-phase microextraction fibres, extraction and desorption conditions were tested in the search of the best linearity, sensitivity and clean-up. The optimal solid-phase microextraction conditions were obtained with a new 65-µm polydimethylsiloxane/divinylbenzene (PDMS/DVB) fibre. Because of the high extraction selectivity and efficiency, the quantification limit for fentanyl and midazolam could be down to 0.8 ng mL−1 and 1 ng mL−1, respectively, for a plasma volume of 1 mL. The method described is sensitive enough for analysed fentanyl and midazolam in plasma samples for toxicological screening and therapeutic drug monitoring.

High Performance Liquid Chromatography Microassay for the Simultaneous Determination of Fentanyl and Its Major Metabolites in Biological Samples

Abstract A simple high performance liquid chromatographic (HPLC) procedure for the simultaneous determination of fentanyl and its wo major metabolites in biological samples was used in blood samples from 6 preterm sick newborn infants. A 8 mm x 100 mm, 4 μm cyano column, 0.05 m phosphate buffer adjusted at pH 3.2 and acetonitrile (50:50 V/V) as mobile phase, were used at a flow rate 2.5 ml/min. Each run was completed within 10 minutes. The detection limits for the analysis were 0.10 ng, 0.15 ng and 0.10 ng for norfentanyl, fentanyl and despropiofentanyl, respectively, with 50 μl injection for all the compounds at a signal-to-noise ratio of 3. The respective retention times were 4.62±0.10, 6.20±0.76 and 6.71±0.73 minutes for norfentanyl, fentanyl and despropiofentanyl. Microassay is simple, rapid and precise. This assay may be used for the therapeutic drug monitoring in newborn babies.

Determination of Fentanyl in Hair: The Case of the Crooked Criminalist

When a State Crime Laboratory Director found that fentanyl patches were missing from a case submission stored in his evidence vault, he performed an investigation of those members of his staff who had access to the materials. As part of this investigation, two staff members were forced to submit to hair testing for fentanyl and other opiates and opioids. This unusual testing protocol was used to identify a senior Criminalist as a chronic abuser of fentanyl, and led to the rapid resolution of the case. To the best of our knowledge, this is the first report of the forensic analysis of hair for drugs of abuse in which the technology was used to identify an individual as a chronic fentanyl abuser.

High-performance Liquid Chromatographic Determination of Fentanyl and Sufentanil Returned from the Operating Room

High-performance Liquid Chromatographic Determination of Fentanyl and Sufentanil Returned from the Operating Room

Determination of fentanyl and alfentanil in plasma by high-performance liquid chromatography with ultraviolet detection

Determination of fentanyl and alfentanil in plasma by high-performance liquid chromatography with ultraviolet detection

Determination of fentanyl and related compounds by capillary gas chromatography with electron capture detection.

Determination of fentanyl and related compounds by capillary gas chromatography with electron capture detection.