Metizolam
(Synonyms: Desmethyletizolam) 目录号 : GC47666An Analytical Reference Standard
Cas No.:40054-68-0
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
Metizolam is an analytical reference standard categorized as a benzodiazepine.1 This product is intended for research and forensic applications.
1.Kintz, P., Richeval, C., Jamey, C., et al.Detection of the designer benzodiazepine metizolam in urine and preliminary data on its metabolismDrug Test. Anal.9(7)1026-1033(2017)
| Cas No. | 40054-68-0 | SDF | |
| 别名 | Desmethyletizolam | ||
| Canonical SMILES | CCC1=CC(C(C2=CC=CC=C2Cl)=NC3)=C(S1)N4C3=NN=C4 | ||
| 分子式 | C16H13ClN4S | 分子量 | 328.8 |
| 溶解度 | DMF: 15mg/mL,DMSO: 15mg/mL,DMSO:PBS (pH 7.2) (1:3): 0.25mg/mL | 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 | 3.0414 mL | 15.2068 mL | 30.4136 mL |
| 5 mM | 0.6083 mL | 3.0414 mL | 6.0827 mL |
| 10 mM | 0.3041 mL | 1.5207 mL | 3.0414 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 Metizolam in urine and preliminary data on its metabolism
Drug Test Anal 2017 Jul;9(7):1026-1033.PMID:27671107DOI:10.1002/dta.2099.
Designer benzodiazepines provide an attractive alternative to prescribed benzodiazepines for abuse purposes as they are readily available via the Internet without control. Metizolam was ordered via the Internet and a 2 mg blue tablet was orally administered to a 54-year-old man. Urine samples were collected over 6 days in polypropylene tubes. After liquid/liquid extraction at pH 9.5, Metizolam was analyzed by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) using a standard method devoted to benzodiazepines, and ions transitions, at m/z 328.9 > 275.0 and 328.9 > 300.0. Metizolam was detectable in hydrolyzed urine during the 46-h period, with concentrations always lower than 11 ng/mL. About 0.3% of the initial dose was excreted in urines as total unchanged Metizolam during the first 24 h. The most relevant potential CYP- and UGT-dependent metabolites of Metizolam were investigated in vitro using human liver microsome incubation and, subsequently, liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS) analysis. Three mono-hydroxylated metabolites were produced including a hydroxylation compound at the 2-ethyl moiety of Metizolam (M1) as quantitatively main metabolite, and a N-hydroxymetiazolam (M2). The structure of the third metabolite (M3) could not be elucidated because of a too low experimental production rate. Two authentic urine samples were analyzed using the same analytical method to search for metabolites of Metizolam. M1, together with its glucuronide (M1-Glu), and M2 were observed in urine at the 8 h mark, whereas only M1 and M1-Glu were still detected in urine at 30 h post administration. Copyright © 2016 John Wiley & Sons, Ltd.
Designer benzodiazepines' pharmacological effects and potencies: How to find the information
J Psychopharmacol 2020 Sep;34(9):1021-1029.PMID:31971477DOI:10.1177/0269881119901096.
Background: Scientific data on the psychopharmacological effects of new psychoactive substances (NPSs) are scarce. Web fora contain a wealth of information posted by users as trip reports (TRs), but the reliability of the reports remains questionable because of the nature of the used molecule and the potential for dose inaccuracies. We focused on the TRs of designer benzodiazepine (DBZD) users since their psychopharmacological effects are similar to prescription benzodiazepines (BZDs). Moreover, the impact of functional groups on the BZD rings with regards to the potency has been fairly/quite studied, allowing structural analysis. Methods: DBZDs offering more than 15 TRs with at least two accounts on experienced effects were included. Data were analyzed with the empirical phenomenological psychological method. Reported effects were analyzed and the pharmacological potencies of DBZDs were compared by calculating a 'potency score'. Results: In total, 197 TRs for clonazolam, deschloroetizolam, diclazepam, etizolam, flubromazepam, flubromazolam, meclonazepam, Metizolam, nifoxipam and pyrazolam were analyzed. Effects similar to prescription BZDs were reported for all the selected DBZDs. Pyrazolam was reported to be the most anxiolytic DBZD, flubromazolam the most hypnotic, etizolam the most euphoric and flubromazolam and clonazolam as the most amnesic DBZDs. Diclazepam and pyrazolam were not reported to induce euphoria. Flubromazepam, flubromazolam, clonazolam and meclonazepam were the most potent and deschloroetizolam, nifoxipam, Metizolam and pyrazolam the least potent. The chemical structure of the different DBZDs and the functional groups on the BZD rings confirmed this ranking, except for nifoxipam. Conclusions: When information on NPSs obtained from Internet fora are abundant, it could be considered as an appreciable data source.
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.
Urine Drug Screening in the Era of Designer Benzodiazepines: Comparison of Three Immunoassay Platforms, LC-QTOF-MS and LC-MS-MS
J Anal Toxicol 2022 Aug 13;46(7):712-718.PMID:34557900DOI:10.1093/jat/bkab108.
This study investigated the presence of designer benzodiazepines in 35 urine specimens obtained from emergency department patients undergoing urine drug screening. All specimens showed apparent false-positive benzodiazepine screening results (i.e., confirmatory testing using a 19-component liquid chromatography-tandem mass spectrometry (LC-MS-MS) panel showed no prescribed benzodiazepines at detectable levels). The primary aims were to identify the possible presence of designer benzodiazepines, characterize the reactivity of commercially available screening immunoassays with designer benzodiazepines and evaluate the risk of inappropriately ruling out designer benzodiazepine use when utilizing common urine drug screening and confirmatory tests. Specimens were obtained from emergency departments of a single US Health system. Following clinically ordered drug screening using Abbott ARCHITECT c assays and laboratory-developed LC-MS-MS confirmatory testing, additional characterization was performed for investigative purposes. Specifically, urine specimens were screened using two additional assays (Roche cobas c502 and Siemens Dimension Vista) and LC-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) to identify presumptively positive species, including benzodiazepines and non-benzodiazepines. Finally, targeted, qualitative LC-MS-MS was performed to confirm the presence of 12 designer benzodiazepines. Following benzodiazepine detection using the Abbott ARCHITECT, benzodiazepines were subsequently detected in 28/35 and 35/35 urine specimens using Siemens and Roche assays, respectively. LC-QTOF-MS showed the presumptive presence of at least one non-Food and Drug Administration (FDA)-approved benzodiazepine in 30/35 specimens: flubromazolam (12/35), flualprazolam (11/35), flubromazepam (2/35), clonazolam (4/35), etizolam (9/35), Metizolam (5/35), nitrazepam (1/35) and pyrazolam (1/35). Two or three designer benzodiazepines were detected concurrently in 13/35 specimens. Qualitative LC-MS-MS confirmed the presence of at least one designer benzodiazepine or metabolite in 23/35 specimens, with three specimens unavailable for confirmatory testing. Urine benzodiazepine screening assays from three manufacturers were cross-reactive with multiple non-US FDA-approved benzodiazepines. Clinical and forensic toxicology laboratories using traditionally designed LC-MS-MS panels may fail to confirm the presence of non-US FDA-approved benzodiazepines detected by screening assays, risking inappropriate interpretation of screening results as false positives.