Metacetamol
(Synonyms: N-(3-羟基苯基)乙酰胺) 目录号 : GC49065A derivative of acetaminophen
Cas No.:621-42-1
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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Metacetamol is a derivative of acetaminophen .1,2,3 Unlike acetaminophen, metacetamol is not cytotoxic to isolated mouse hepatocytes (LC50 = >10 mM).1 However, it does induce necrosis and depletion of glutathione (GSH) in isolated human hepatocytes when used at a concentration of 10 mM.2 Metacetamol (900 mg/kg) does not induce hepatic necrosis in mice.3
1.Holme, J.A., Hongslo, J.K., BjØrge, C., et al.Comparative cytotoxic effects of acetaminophen (N-acetyl-p-aminophenol), a non-hepatotoxic regioisomer acetyl-m-aminophenol and their postulated reactive hydroquinone and quinone metabolites in monolayer cultures of mouse hepatocytesBiochem. Pharmacol.42(5)1137-1142(1991) 2.Xie, Y., McGill, M.R., Du, K., et al.Mitochondrial protein adducts formation and mitochondrial dysfunction during N-acetyl-m-aminophenol (AMAP)-induced hepatotoxicity in primary human hepatocytesToxicol. Appl. Pharmacol.289(2)213-222(2015) 3.Nelson, E.B.The pharmacology and toxicology of meta-substituted acetanilide I: Acute toxicity of 3-hydroxyacetanilide in miceRes. Commun. Chem. Pathol. Pharmacol.28(3)447-456(1980)
Cas No. | 621-42-1 | SDF | |
别名 | N-(3-羟基苯基)乙酰胺 | ||
Canonical SMILES | O=C(C)NC1=CC(O)=CC=C1 | ||
分子式 | C8H9NO2 | 分子量 | 151.2 |
溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:4): 0.20 mg/ml,Ethanol: 5 mg/ml | 储存条件 | -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 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 6.6138 mL | 33.0688 mL | 66.1376 mL |
5 mM | 1.3228 mL | 6.6138 mL | 13.2275 mL |
10 mM | 0.6614 mL | 3.3069 mL | 6.6138 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 | ||||||||||
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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。
A novel crystal form of Metacetamol: the first example of a hydrated form
Acta Crystallogr C Struct Chem 2019 Nov 1;75(Pt 11):1465-1470.PMID:31686655DOI:10.1107/S2053229619012981.
We report the crystal structure and crystallization conditions of a first hydrated form of Metacetamol (a hemihydrate), C8H9NO2·0.5H2O. It crystallizes from metacetamol-saturated 1:1 (v/v) water-ethanol solutions in a monoclinic structure (space group P21/n) and contains eight Metacetamol and four water molecules per unit cell. The conformations of the molecules are the same as in polymorph II of Metacetamol, which ensures the formation of hydrogen-bonded dimers and R22(16) ring motifs in its crystal structure similar to those in polymorph II. Unlike in form II, however, these dimers in the hemihydrate are connected through water molecules into infinite hydrogen-bonded molecular chains. Different chains are linked to each other by metacetamol-water and metacetamol-metacetamol hydrogen bonds, the latter type being also present in polymorph I. The overall noncovalent network of the hemihydrate is well developed and several types of hydrogen bonds are responsible for its formation.
The Pressure-Temperature Phase Diagram of Metacetamol and Its Comparison to the Phase Diagram of Paracetamol
J Pharm Sci 2017 Jun;106(6):1538-1544.PMID:28192078DOI:10.1016/j.xphs.2017.02.003.
Understanding the polymorphic behavior of active pharmaceutical ingredients is important for formulation purposes and regulatory reasons. Metacetamol is an isomer of paracetamol and it similarly exhibits polymorphism. In the present article, it has been found that one of the polymorphs of Metacetamol is only stable under increased pressure, which has led to the conclusion that Metacetamol like paracetamol is a monotropic system under ordinary (= laboratory) conditions and that it becomes enantiotropic under pressure with the I-II-L triple point coordinates for Metacetamol TI-II-L = 535 ± 10 K and PI-II-L = 692 ± 70 MPa. However, whereas for paracetamol the enantiotropy under pressure can be foreseen, because the metastable polymorph is denser, in the case of Metacetamol this is not possible, as the metastable polymorph is less dense than the stable one. The existence of the stability domain for the less dense polymorph of Metacetamol can only be demonstrated by the construction of the topological phase diagram as presented in this article. It is a delicate interplay between the specific volume differences and the enthalpy differences causing the stability domain of the less dense polymorph to be sandwiched between the denser polymorph and the liquid. Metacetamol shares this behavior with bicalutamide and fluoxetine nitrate.
Quantitative analysis of paracetamol, Metacetamol, and orthocetamol in equine urine from racehorses in Japan using liquid chromatography-electrospray ionization-tandem mass spectrometry
Drug Test Anal 2020 Aug;12(8):1196-1202.PMID:32436292DOI:10.1002/dta.2860.
Paracetamol is commonly used as an over-the-counter analgesic and antipyretic medication for humans, but not sold as a legitimate therapeutic medication for horses in Japan. However, paracetamol is commonly found in horses together with its two isomers, Metacetamol and orthocetamol. We previously reported that paracetamol and orthocetamol were both present in selected feed consumed by Japanese racehorses. For the purpose of the doping control of paracetamol in local Japanese horses, we proposed establishing residue limits (Japanese residue limits, JRLs) to minimize the risk of reporting paracetamol from environmental contributions and to differentiate its presence from active administration. Recently, we proposed a preliminary JRL for paracetamol in equine plasma based on a population study of more than 300 Japanese racehorses. In this paper, we will present our studies on the urinary concentrations of paracetamol, Metacetamol, and orthocetamol in postrace samples collected from 403 Japanese racehorses over a 1 year period, detected using liquid chromatography-electrospray ionization-tandem mass spectrometry. Our results revealed that the hydrolyzed urinary concentrations of paracetamol, Metacetamol, and orthocetamol were in the range 15.7-2,360 ng/mL (median 363 ng/mL), 8.07-382 ng/mL (84.5 ng/mL), and 919-74,418 ng/mL (13,475 ng/mL), respectively. Based on our statistical model, the preliminary JRL of hydrolyzed paracetamol in equine urine was determined to be 7,400 ng/mL, at a risk factor of 1 in 10,000. Further investigations will be required to demonstrate the applicability and validity of our preliminary plasma and urine JRLs to local Japanese racehorses.
Investigation of plasma concentrations of paracetamol, Metacetamol, and orthocetamol in Japanese racehorses using liquid chromatography-electrospray ionisation-tandem mass spectrometry
Drug Test Anal 2020 Jul;12(7):929-937.PMID:32187884DOI:10.1002/dta.2792.
Paracetamol is used widely as an over-the-counter analgesic and antipyretic medication for humans, but not for Japanese racehorses. Paracetamol can be an environmental substance, and is found together with its two isomers, Metacetamol and orthocetamol, in equine urine. However, the sources and routes of paracetamol exposure remain unclear. To control the misuse of paracetamol, it is appropriate to establish residue limits for paracetamol to differentiate the administration of paracetamol from its environmental levels. In this study, we developed and validated a quantitative method for paracetamol, Metacetamol, and orthocetamol in equine plasma using liquid chromatography-electrospray ionization-tandem mass spectrometry and applied it to postrace samples from 320 Japanese racehorses for approximately 1 year. In addition, we conducted feed analysis and related pharmacokinetics simulations to evaluate the contributions from exposure via feed. The hydrolyzed plasma concentrations of paracetamol, Metacetamol, and orthocetamol ranged from 0.787 to 39.8 ng/mL (median 5.87 ng/mL), 0 to 2.13 ng/mL (0.347 ng/mL), and 1.98 to 82.8 ng/mL (16.6 ng/mL), respectively. Such low concentrations of paracetamol were deemed irrelevant to therapeutic effect. Based on statistical analysis, the preliminary Japanese residue limits of unhydrolyzed and hydrolyzed paracetamol were determined to be 70.5 ng/mL and 112 ng/mL, respectively, in plasma, at a risk factor of 1 in 10,000. Furthermore, we detected paracetamol and orthocetamol in feed samples. A pharmacokinetics simulation showed that the presence of orthocetamol is most probably related to daily feed rations. As for paracetamol, feed can be one of the sources and other possible sources require further investigation.
A Novel Drug-Drug Cocrystal of Levofloxacin and Metacetamol: Reduced Hygroscopicity and Improved Photostability of Levofloxacin
J Pharm Sci 2019 Jul;108(7):2383-2390.PMID:30807761DOI:10.1016/j.xphs.2019.02.014.
Levofloxacin (LVFX), a broad-spectrum antibacterial agent from the fluoroquinolone family, is universally prescribed with antipyretics, including paracetamol (APAP) analogs. In this study, a new drug-drug cocrystal of LVFX and an APAP analog was developed using a grinding and heating approach. Among 9 APAP analogs, only Metacetamol (AMAP) was able to form a cocrystal with LVFX, with a stoichiometric ratio of 1:1. This cocrystal was obtained from a eutectic melt of anhydrous LVFX and AMAP after complete desorption of water from LVFX hemihydrate. The crystal structure of the cocrystal was determined by single-crystal X-ray structural analysis. Unlike LVFX hydrates, the LVFX-AMAP cocrystal did not form a channel structure where water molecules reside in LVFX hydrates. Thus, the LVFX-AMAP cocrystal did not undergo hydration under high relative humidity conditions during vapor sorption-desorption analysis and physical stability tests. LVFX photostability was improved by cocrystallization when compared with that of the hemihydrate because of hydrogen bond formation between the hydroxyl group of AMAP and the N-methylpiperazine group of LVFX, which is possibly involved in LVFX photodegradation. The LVFX-AMAP cocrystal, which is superior to LVFX hydrates in both pharmacological and physicochemical properties, is expected to be a useful solid form.