Simultaneous quantification of fentanyl,sufentanil, cefazolin,doxapram and keto‐doxapram in plasma using liquid chromatography–tandem mass spectrometry

A simple and specific UPLC–MS/MS method was developed and validated for simultaneous quantification of fentanyl, sufentanil, cefazolin, doxapram and its active metabolite keto‐doxapram. The internal standard was fentanyl‐d5 for all analytes. Chromatographic separation was achieved with a reversed‐phase Acquity UPLC HSS T3 column with a run‐time of only 5.0 min per injected sample. Gradient elution was performed with a mobile phase consisting of ammonium acetate or formic acid in Milli‐Q ultrapure water or in methanol with a total flow rate of 0.4 mL min⁻¹. A plasma volume of only 50 μL was required to achieve adequate accuracy and precision. Calibration curves of all five analytes were linear. All analytes were stable for at least 48 h in the autosampler. The method was validated according to US Food and Drug Administration guidelines. This method allows quantification of fentanyl, sufentanil, cefazolin, doxapram and keto‐doxapram, which is useful for research as well as therapeutic drug monitoring, if applicable. The strength of this method is the combination of a small sample volume, a short run‐time, a deuterated internal standard, an easy sample preparation method and the ability to simultaneously quantify all analytes in one run.     

液相色谱-四极杆/飞行时间质谱法分析29种芬太尼类物质及其碎裂机理北大核心CSCD

芬太尼类物质品种繁多,自我国整类列管后,整类检测是该领域的重点和难点。该文详细研究了29种化合物的二级质谱碎片离子碎裂机理,总结出芬太尼类物质的碎裂规律和特点,为芬太尼物质的整类筛查检测提供参考。建立了分析29种芬太尼类物质的一级和二级质谱库的定性方法,建立了液相色谱-四极杆/飞行时间质谱(LC-QTOF-MS)检测29种芬太尼类物质的定量方法。药品和白色粉末类、蛋白质和乳饮料类样品经乙腈提取,含糖固体或粉末类、饮用水类、果蔬饮料类、保健饮料类、茶饮料类、酒类样品经10%乙腈水溶液提取,提取液经涡旋、离心和过膜后,采用Kinetex C18色谱柱(100 mm×2.1 mm,2.6μm)分离,以乙腈和0.08%甲酸水溶液为流动相进行梯度洗脱,采用四极杆/飞行时间质谱,在正离子模式下,外标法定量检测。结果表明,29种芬太尼类物质在1~20μg/L范围内线性关系良好,相关系数均大于0.995,检出限(LOQ)均为0.01 mg/kg,定量限(LOQ)均为0.05 mg/kg,在降糖药、露露、葡萄糖粉、珍露保健饮料和巧克力样品中3个加标水平平均回收率为85.2%~112.9%,相对标准偏差(RSD)为1.9%~19.8%(n=6)。该方法操作简单,耗时短,灵敏度高,稳定性好,检测品种覆盖范围广,适用于药品类、含糖固体或粉末类、饮料类、饮用水类和酒类等样品中29芬太尼类物质的定性和定量检测。     

Preparation of bamboo-derived magnetic biochar for solid-phase microextraction of fentanyls from urine

In this study, a biochar-based magnetic solid-phase microextraction method, coupled with liquid chromatography–mass spectrometry, was developed for analyzing fentanyl analogs from urine sample. Magnetic biochar was fabricated through a one-step pyrolysis carbonization and magnetization process, followed by an alkali treatment. In order to achieve desired extraction efficiency, feed stocks (wood and bamboo) and different pyrolysis temperatures (300–700°C) were optimized. The magnetic bamboo biochar pyrolyzed at 400°C was found to have the greatest potential for extraction of fentanyls, with enrichment factors ranging from 58.9 to 93.7, presumably due to H-bonding and π–π interactions between biochar and fentanyls. Various extraction parameters, such as type and volume of desorption solvent, pH, and extraction time, were optimized, respectively, to achieve the highest extraction efficiency for the target fentanyls. Under optimized conditions, the developed method was found to have detection limits of 3.0–9.4 ng/L, a linear range of 0.05–10 μg/L, good precisions (1.9–9.4% for intrabatch, 2.9–9.9% for interbatch), and satisfactory recoveries (82.0–111.3%). The developed method by using magnetic bamboo biochar as adsorbent exhibited to be an efficient and promising pretreatment procedure and could potentially be applied for drug analysis in biological samples.     

生物检材中芬太尼类物质检测方法研究进展

就芬太尼类物质的代谢及近年来对常见生物检材中此类物质的前处理方法及检测方法进行了综述.常见的生物检材有血液、尿液、毛发,这几种检材都具有各自的检测优势和不足.毒品在血液中代谢速度快,代谢产物浓度高,但对检测时效性要求较高;尿液检测前处理简单,代谢产物易检测,但存在易污染、造假的问题;毛发检测不受其他药物影响,可追溯半年...     

Detection of fentanyl in binary mixtures with cocaine by use of surface-enhanced Raman spectroscopy

Abstract

The ongoing epidemic pertaining to overdose deaths has been attributed to the synthetic opioid fentanyl due to its use as an adulterant in other, less potent drugs of abuse. Detection of low quantities of fentanyl would, therefore, be extremely useful in a forensic science laboratory. While Raman spectroscopy is particularly effective at distinguishing between classes of drugs, weak signatures can prove difficult when dealing with microscopic samples. Surface-enhanced Raman scattering spectroscopy provides the enhancement necessary to make Raman a viable approach for the detection of small amounts of fentanyl. This work explores the use of a paper-based substrate loaded with silver nanoparticles for the recovery of small quantities of fentanyl in cocaine, where it was identified at a lower limit of 500?ng (～65?ppm) in mixtures. Linear relationships were investigated between intensity and concentration for diagnostic peaks associated with fentanyl and cocaine, which in turn sheds light on the attenuation of the enhancement intensity as a result of competitive binding to silver nanoparticles. This work demonstrates a potentially simple and qualitative pathway for the forensic analysis of fentanyl as an adulterant in cocaine.     

Lipemia in the Plasma Sample Affects Fentanyl Measurements by Means of HPLC-MS2 after Liquid-Liquid Extraction

Examination of fentanyl levels is frequently performed in certain scientific evaluations and forensic toxicology. It often involves the collection of very variable blood samples, including lipemic plasma or serum. To date, many works have reported the methods for fentanyl detection, but none of them have provided information about the impact on the assay performance caused by an excessive amount of lipids. This aspect may be, however, very important for highly lipophilic drugs like fentanyl. To address this issue, we developed the liquid chromatography method with mass spectrometry detection and utilized it to investigate the impact of lipids presence in rabbit plasma on the analytical method performance and validation. The validation procedure, conducted for normal plasma and lipemic plasma separately, resulted in good selectivity, sensitivity and linearity. The limits of detection and quantification were comparable between the two matrices, being slightly lower in normal plasma (0.005 and 0.015 µg/L) than in lipemic plasma (0.008 and 0.020 µg/L). Liquid–liquid extraction provided a low matrix effect regardless of the lipid levels in the samples (<10%), but pronounced differences were found in the recovery and accuracy. In the normal plasma, this parameter was stable and high (around 100%), but in the lipemic matrix, much more variable and less efficient results were obtained. Nevertheless, this difference had no impact on repeatability and reproducibility. In the present work, we provided reliable, convenient and sensitive method for fentanyl detection in the normal and lipemic rabbit plasma. However, construction of two separate validation curves was necessary to provide adequate results since the liquid-liquid extraction was utilized. Therefore, special attention should be paid during fentanyl quantification that involves lipemic plasma samples purified by this technique.     

Preparation of Fentanyl Analogs Suitable For Immobilization For Receptor Binding Analyses

Abstract

The synthesis and characterization of amino and azide fentanyl derivatives is described. Provision for radiolabeling the azide derivative also is included. These compounds were selected since they can easily undergo immobilization onto glass supports for a planned study to use infrared spectroscopy to analyze fentanyl binding to opiate receptors.     

Synthesis of amides from imines using Et3SiH/Zn system

A simple and efficient approach for the synthesis of amides by the reaction of imines and acyl chlorides in the presence of Et₃SiH/Zn system in THF at ambient temperature is reported. Mild reaction conditions, good yields of products, short reaction time and operational simplicity are the advantages of this procedure. Copyright © 2012 John Wiley & Sons, Ltd.     

Hyperpolarization of Pyridyl Fentalogues by Signal Amplification By Reversible Exchange (SABRE)

Fentanyl, also known as ‘jackpot’, is a synthetic opiate that is 50–100 times more potent than morphine. Clandestine laboratories produce analogues of fentanyl, known as fentalogues to circumvent legislation regarding its production. Three pyridyl fentalogues were synthesized and then hyperpolarized by signal amplification by reversible exchange (SABRE) to appraise the forensic potential of the technique. A maximum enhancement of -168-fold at 1.4 T was recorded for the ortho pyridyl ¹H nuclei. Studies of the activation parameters for the three fentalogues revealed that the ratio of ligand loss trans to hydride and hydride loss in the complex [Ir(IMes)(L)₃(H)₂]⁺ (IMes=1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene) ranged from 0.52 to 1.83. The fentalogue possessing the ratio closest to unity produced the largest enhancement subsequent to performing SABRE at earth's magnetic field. It was possible to hyperpolarize a pyridyl fentalogue selectively from a matrix that consisted largely of heroin (97 : 3 heroin:fentalogue) to validate the use of SABRE as a forensic tool.     

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.