Flunitrazolam
目录号 : GC43680An Analytical Reference Standard
Cas No.:2243815-18-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Flunitrazolam is an analytical reference standard categorized as a benzodiazepine. [1] Flunitrazolam has been found in biological samples from intoxication cases.[2] This product is intended for research and forensic applications.
Reference:
[1]. Ameline, A., Richeval, C., Gaulier, J.M., et al. Characterization of flunitrazolam, a new designer benzodiazepine, in oral fluid after a controlled single administration. J. Anal. Toxicol. (2018).
[2]. Helander, A., Bäckberg, M., Signell, P., et al. Intoxications involving acrylfentanyl and other novel designer fentanyls - results from the Swedish STRIDA project. Clin. Toxicol. (Phila) 55(6), 589-599 (2017).
| Cas No. | 2243815-18-9 | SDF | |
| 化学名 | 6-(2-fluorophenyl)-1-methyl-8-nitro-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine | ||
| Canonical SMILES | CC1=NN=C2CN=C(C3=CC=CC=C3F)C4=C(C=CC([N+]([O-])=O)=C4)N21 | ||
| 分子式 | C17H12FN5O2 | 分子量 | 337.3 |
| 溶解度 | 20mg/mL in DMSO, 30mg/mL in DMSO, 10mg/mL in Ethanol | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9647 mL | 14.8236 mL | 29.6472 mL |
| 5 mM | 0.5929 mL | 2.9647 mL | 5.9294 mL |
| 10 mM | 0.2965 mL | 1.4824 mL | 2.9647 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Detection of the designer benzodiazepine Flunitrazolam in urine and preliminary data on its metabolism
Drug Test Anal 2019 Feb;11(2):223-229.PMID:30109775DOI:10.1002/dta.2480.
Designer benzodiazepines have emerged as recreational drugs. They are available via the Internet without control and are found in the form of falsified (fake) medicines. For some of them, limited information concerning their effects, their toxicity, and their detection in bio fluids is available in the literature. For others, nothing has been published, as in the case of Flunitrazolam (FNTZ). To gain preliminary data on its elimination parameters in urine and to investigate its metabolism, one of the authors ingested one pink tablet bought on the Internet, after confirming the absence of other compounds and agreement with the labeled dosage (0.25 mg) by nuclear magnetic resonance (NMR). A software algorithm (MetaboLynx, Waters, Milford, MA, USA) was used to predict FNTZ biotransformation and four potential metabolites were proposed: 4-hydroxy-FNTZ, desnitro-FNTZ, 7-amino-FNTZ, and 7-acetamido-FNTZ. Urine samples were collected over 72 hours following oral administration of one tablet. After liquid/liquid extraction at pH 9.5, FNTZ concentrations were determined using ultra performance liquid chromatography-triple quadrupole-mass spectrometry (UPLC-QqQ-MS/MS). FNTZ remained detectable in hydrolyzed urine for 21 hours after ingestion, with concentrations ranging between 1 and 18 ng/mL. About 3% of the initial dose was excreted in urine as total unchanged FNTZ during this period. In vitro experiments (HLM incubations) were performed using ultra performance liquid chromatography-quadrupole time of flight-mass spectrometry (UPLC-QTOF-MS) in order to investigate the potential CYP- and UGT-dependent metabolites where only 7-amino-FNTZ was detected as the only metabolite. However, in the urine specimens, desnitro-FNTZ, 7-acetamido-FNTZ and 7-amino-FNTZ were the main detected compounds. The identification of FNTZ metabolites dramatically improves the detection windows of the drug up to 37 hours.
Characterization and in vitro phase I microsomal metabolism of designer benzodiazepines: An update comprising Flunitrazolam, norflurazepam, and 4'-chlorodiazepam (Ro5-4864)
Drug Test Anal 2019 Mar;11(3):541-549.PMID:30578721DOI:10.1002/dta.2561.
The number of newly appearing benzodiazepine derivatives on the new psychoactive substances (NPS) drug market has increased over the last couple of years totaling 23 'designer benzodiazepines' monitored at the end of 2017 by the European Monitoring Centre for Drugs and Drug Addiction. In the present study, three benzodiazepines [Flunitrazolam, norflurazepam, and 4'-chlorodiazepam (Ro5-4864)] offered as 'research chemicals' on the Internet were characterized and their main in vitro phase I metabolites tentatively identified after incubation with pooled human liver microsomes. For all compounds, the structural formula declared by the vendor was confirmed by gas chromatography-mass spectrometry (GC-MS), liquid chromatography-tandem mass spectrometry (LC MS/MS), liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS) analysis and nuclear magnetic resonance (NMR) spectroscopy. The metabolic steps of Flunitrazolam were monohydroxylation, dihydroxylation, and reduction of the nitro function. The detected in vitro phase I metabolites of norflurazepam were hydroxynorflurazepam and dihydroxynorflurazepam. 4'-Chlorodiazepam biotransformation consisted of N-dealkylation and hydroxylation. It has to be noted that 4'-chlorodiazepam and its metabolites show almost identical LC-MS/MS fragmentation patterns to diclazepam and its metabolites (delorazepam, lormetazepam, and lorazepam), making a sufficient chromatographic separation inevitable. Sale of norflurazepam, the metabolite of the prescribed benzodiazepines flurazepam and fludiazepam, presents the risk of incorrect interpretation of analytical findings.
The Development and Validation of a Novel Designer Benzodiazepines Panel by LC-MS-MS
J Anal Toxicol 2021 May 14;45(5):423-428.PMID:33476376DOI:10.1093/jat/bkab013.
Novel illicit benzodiazepines are among the most active areas of new illicit drug manufacture and use. We describe a method for the detection and quantification of etizolam and its metabolite α-hydroxyetizolam, flubromazolam, clonazolam, diclazepam, delorazepam, bromazepam, flubromazepam, phenazepam, flualprazolam, Flunitrazolam, and nitrazolam in human whole blood. After addition of internal standards, samples are buffered and extracted using a liquid-liquid extraction. Analysis is performed using positive-ion electrospray tandem mass spectrometry for detection and quantitation. Calibration ranges were established based on the method performance and differed from compound to compound. Replicates at the lowest calibration point for each compound performed within 5% of CV (Coefficient of Variation). The correlation coefficient was >0.990 for all compounds. Relative standard deviation for all compounds was ≤10% of CV and accuracy was ±10% for both within- and between-run experiments. The maximum average intra- and inter-run imprecision were 5.7%. The maximum average intra- and inter-run imprecision was -8.7%. As part of evaluating the scope for relevancy, samples testing positive in immunoassay but confirmed to be negative in traditional benzodiazepine confirmation method were re-analyzed using this method. The presence of at least one novel benzodiazepine was identified in 70% of these samples. The appearance of these novel "designer" benzodiazepines demonstrates the challenge for toxicology testing and the need for continually updated confirmation methods.
In vitro glucuronidation of designer benzodiazepines by human UDP-glucuronyltransferases
Drug Test Anal 2019 Jan;11(1):45-50.PMID:29996009DOI:10.1002/dta.2463.
Multiple new psychoactive substances (NPS) are released into the recreational drug market each year. One NPS drug class that has become more common in recent years is that of the benzodiazepines (designer benzodiazepines, DBZ). Several metabolism studies have been performed to improve their bioanalytical detection via the best target. These studies have shown the presence of parent glucuronides and, as polymorphisms have been noted for the catalyzing enzymes (UDP-glucuronyltransferases) responsible for glucuronide conjugation reactions, it is important to keep this in mind when interpreting DBZ cases in clinical and/or forensic toxicology. Therefore, the aim of this study was to determine the UDP-glucuronyltransferases (UGTs) responsible for parent compound conjugation of nine DBZ to facilitate interpretation of related cases. Clonazolam, deschloroetizolam, etizolam, flubromazolam, Flunitrazolam, metizolam, nifoxipam, nitrazolam, and pyrazolam were incubated with pooled human liver microsomes (pHLM) or 13 different human UGTs. The samples were analyzed using liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS). Glucuronide conjugates of Flunitrazolam and nifoxipam were only detected in pHLM, suggesting that these reactions are performed by dimer complexes of several UGTs or complexes between UGTs and other metabolizing enzymes contained in pHLM. Nitrazolam or pyrazolam glucuronides were not detected. Glucuronidation of clonazolam, deschloroetizolam, etizolam, flubromazolam, and metizolam was catalyzed exclusively by UGT1A4. The conjugation of the majority of the DBZ was performed by the UGT isoform 1A4 for which polymorphisms have been described. This underlines the importance of taking glucuronidation polymorphism into consideration when interpreting intoxication cases.
Validation of an LC-MS/MS Method for the Quantification of 13 Designer Benzodiazepines in Blood
J Anal Toxicol 2019 Oct 17;43(9):688-695.PMID:31436813DOI:10.1093/jat/bkz063.
The misuse of designer benzodiazepines, as an alternative to prescription benzodiazepines and for drug-facilitated sexual assaults, has emerged as a growing threat, due in part to the ease of purchasing these drugs on the internet at low prices. Causing concern for safety is the lack of dosage information resulting in users self-medicating, often leading to unintended overdoses, coma or death at higher doses. With limited published data regarding the quantification of designer benzodiazepines in forensic cases, a method was validated for the determination of 13 designer benzodiazepines in postmortem blood, to add to the in-house method that already included a limited number of common designer benzodiazepines. The developed method included 3-hydroxyphenazepam, clobazam, clonazolam, delorazepam, deschloroetizolam, diclazepam, flualprazolam, flubromazepam, flubromazolam, Flunitrazolam, meclonazepam, nifoxipam and pyrazolam in 0.5 mL postmortem blood using liquid chromatography-tandem mass spectrometry. The analytes were treated with solid phase extraction before undergoing separation on a C18 column and analyzed on the mass spectrometer in electrospray positive mode using multiple reaction monitoring. The linear range of the calibration curve was 1-200 ng/mL and up to 500 ng/mL for 3-hydroxyphenazepam, clobazam, flubromazepam and pyrazolam. The limits of detection and quantitation were 0.5 ng/mL (signal-to-noise ratio >3) and 1 ng/mL, respectively. The calculated bias, intra-day imprecision, relative standard deviation (RSD) and inter-day imprecision RSD were ±12%, 3-20% and 4-21%. Matrix effects ranged from -52% to 33% with RSD values ranging from 3-20%, indicating consistent effects throughout multiple sources. Recovery ranged from 35 to 90%, where only two compounds were <50%. Other parameters tested included carryover, stability, interference and dilution integrity, which all yielded acceptable results. With the application of this method to blood specimens from the New York City Office of Chief Medical Examiner, this validated method proved to be simple, reproducible, sensitive and robust.