Nitrazolam
(Synonyms: 硝唑仑) 目录号 : GC41512An Analytical Reference Standard
Cas No.:28910-99-8
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
Nitrazolam is an analytical reference standard categorized as a benzodiazepine. [1] This product is intended for research and forensic applications.
Reference:
[1]. Hester, J.B., Jr., Rudzik, A.D., and Kamidar, B.V. 6-Phenyl-4H-s-triazolo[4,3-α][1,4]benzodiazepines which have central nervous system depressant activity. J. Med. Chem. 14(11), 1078-1081 (1971).
| Cas No. | 28910-99-8 | SDF | |
| 别名 | 硝唑仑 | ||
| 化学名 | 1-methyl-8-nitro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine | ||
| Canonical SMILES | CC1=NN=C2CN=C(C3=CC=CC=C3)C4=C(C=CC([N+]([O-])=O)=C4)N21 | ||
| 分子式 | C17H13N5O2 | 分子量 | 319.3 |
| 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 | 3.1319 mL | 15.6593 mL | 31.3185 mL |
| 5 mM | 0.6264 mL | 3.1319 mL | 6.2637 mL |
| 10 mM | 0.3132 mL | 1.5659 mL | 3.1319 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。
An approach to shortening the timeframe between the emergence of new compounds on the drugs market and the availability of reference standards: The microscale syntheses of Nitrazolam and clonazolam for use as reference materials, utilizing polymer-supported reagents
Drug Test Anal 2018 Mar 15.PMID:29542872DOI:10.1002/dta.2383.
Nitrazolam and clonazolam are 2 designer benzodiazepines available from Internet retailers. There is growing evidence suggesting that such compounds have the potential to cause severe adverse events. Information about tolerability in humans is scarce but typically, low doses can be difficult to administer for users when handling bulk material. Variability of the active ingredient in tablet formulations can also be of a concern. Customs, toxicology and forensic laboratories are increasingly encountering designer benzodiazepines, both in tablet and powdered form. The unavailability of reference standards can impact on the ability to identify these compounds. Therefore, the need arises for exploring in-house approaches to the preparation of new psychoactive substances (NPS) that can be carried out in a timely manner. The present study was triggered when samples of clonazolam were received in powdered and tablet form at a time when reference material for this drug was commercially unavailable. Therefore, microscale syntheses of clonazolam and its deschloro analog Nitrazolam were developed utilizing polymer-supported reagents starting from 2-amino-2'-chloro-5-nitrobenzophenone (clonazolam) and 2-amino-5-nitrobenzophenone (Nitrazolam). The final reaction step forming the 1,2,4-triazole ring moiety was performed within a gas chromatography-mass spectrometry (GC-MS) injector. A comparison with a preparative scale synthesis of both benzodiazepine derivatives showed that microscale synthesis might be an attractive option for a forensic laboratory in terms of time and cost savings when compared with traditional methods of synthesis and when qualitative identifications are needed to direct forensic casework. The reaction by-product profiles for both the micro and the preparative scale syntheses are also presented.
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.
Characterization and in vitro phase I microsomal metabolism of designer benzodiazepines - an update comprising adinazolam, cloniprazepam, fonazepam, 3-hydroxyphenazepam, metizolam and Nitrazolam
J Mass Spectrom 2016 Nov;51(11):1080-1089.PMID:27535017DOI:10.1002/jms.3840.
Designer benzodiazepines represent an emerging class of new psychoactive substances. While other classes of new psychoactive substances such as cannabinoid receptor agonists and designer stimulants are mainly consumed for hedonistic reasons, designer benzodiazepines may also be consumed as 'self-medication' by persons suffering from anxiety or other psychiatric disorders or as stand-by 'antidote' by users of stimulant and hallucinogenic drugs. In the present study, five benzodiazepines (adinazolam, cloniprazepam, fonazepam, 3-hydroxyphenazepam and Nitrazolam) and one thienodiazepine (metizolam) 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 nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry (MS), liquid chromatography MS/MS and liquid chromatography quadrupole time-of-flight MS analysis. The detected in vitro phase I metabolites of adinazolam were N-desmethyladinazolam and N-didesmethyladinazolam. Metizolam showed a similar metabolism to other thienodiazepines comprising monohydroxylations and dihydroxylation. Cloniprazepam was metabolized to numerous metabolites with the main metabolic steps being N-dealkylation, hydroxylation and reduction of the nitro function. It has to be noted that clonazepam is a metabolite of cloniprazepam, which may lead to difficulties when interpreting analytical findings. Nitrazolam and fonazepam both underwent monohydroxylation and reduction of the nitro function. In the case of 3-OH-phenazepam, no in vitro phase I metabolites were detected. Formation of licensed benzodiazepines (clonazepam after uptake of cloniprazepam) and the sale of metabolites of prescribed benzodiazepines (fonazepam, identical to norflunitrazepam, and 3-hydroxyphenazepam) present the risk of incorrect interpretation of analytical findings. Copyright © 2016 John Wiley & Sons, Ltd.
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.
Designer Benzodiazepines: Another Class of New Psychoactive Substances
Handb Exp Pharmacol 2018;252:383-410.PMID:30367253DOI:10.1007/164_2018_154.
Benzodiazepines have been introduced as medical drugs in the 1960s. They replaced the more toxic barbiturates, which were commonly used for treatment of anxiety or sleep disorders at the time. However, benzodiazepines show a high potential of misuse and dependence. Although being of great value as medicines, dependence to these drugs is a concern worldwide, in part due to overprescription and easy availability. Therefore, the phenomenon of benzodiazepines sold via Internet shops without restrictions at low prices is alarming and poses a serious threat to public health. Most of these compounds (with the exception of, e.g., phenazepam and etizolam) have never been licensed as medical drugs in any part of the world and are structurally derived from medically used benzodiazepines. Strategies of clandestine producers to generate new compounds include typical structural variations of medically used 1,4-benzodiazepines based on structure-activity relationships as well as synthesis of active metabolites and triazolo analogs of these compounds. As they were obviously designed to circumvent national narcotics laws or international control, they can be referred to as "designer benzodiazepines." The majority of these compounds, such as diclazepam, clonazolam, and Nitrazolam, have been described in scientific or patent literature. However, little is known about their pharmacological properties and specific risks related to their use. This chapter describes the phenomenon of designer benzodiazepines and summarizes the available data on pharmacokinetics and pharmacodynamics as well as analytical approaches for their detection.