N-desmethyl Regorafenib N-oxide
(Synonyms: 瑞戈非尼杂质14) 目录号 : GC49686
An active metabolite of regorafenib
Cas No.:835621-12-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >90.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
N-desmethyl Regorafenib N-oxide is an active metabolite of the multi-kinase inhibitor regorafenib .1 It is formed from regorafenib by the cytochrome P450 (CYP) isoform CYP3A4. N-desmethyl Regorafenib N-oxide inhibits VEGFR2, Tie2, c-Kit, and B-RAF in vitro, as well as inhibits tumor growth in HT-29 and MDA-MB-231 mouse xenograft models when administered at a dose of 1 mg/kg.2
1.Li, Y.-H., Lin, Q.-M., Pang, N.-H., et al.Functional characterization of 27 CYP3A4 protein variants to metabolize regorafenib in vitroBasic Clin. Pharmacol. Toxicol.125(4)337-344(2019) 2.Zopf, D., Heinig, R., Thierauch, K.-H., et al.Abstract 1666: Regorafenib (BAY 73-4506): Preclinical pharmacology and clinical identification and quantification of its major metabolitesCancer. Res.70(8 Suppl.)(2010)
| Cas No. | 835621-12-0 | SDF | Download SDF |
| 别名 | 瑞戈非尼杂质14 | ||
| Canonical SMILES | O=C(C1=CC(OC2=CC(F)=C(NC(NC3=CC(C(F)(F)F)=C(Cl)C=C3)=O)C=C2)=CC=[N]1=O)N | ||
| 分子式 | C20H13ClF4N4O4 | 分子量 | 484.8 |
| 溶解度 | DMSO: soluble | 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0627 mL | 10.3135 mL | 20.6271 mL |
| 5 mM | 0.4125 mL | 2.0627 mL | 4.1254 mL |
| 10 mM | 0.2063 mL | 1.0314 mL | 2.0627 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。
A LC-MS/MS method for therapeutic drug monitoring of sorafenib, regorafenib and their active metabolites in patients with hepatocellular carcinoma
J Pharm Biomed Anal 2020 Aug 5;187:113358.PMID:32460216DOI:10.1016/j.jpba.2020.113358.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of sorafenib (SORA), its N-oxide active metabolite and of regorafenib (REGO) and its two active metabolites regorafenib N-oxide and N-desmethyl Regorafenib N-oxide in hepatocellular carcinoma patients' plasma. A proper analytes' separation was obtained with Synergi Fusion RP column (4 μm, 80 ?, 50 × 2.0 mm) using a gradient elution of 10 mM ammonium acetate with 0.1% formic acid (mobile phase A) and methanol:isopropanol (90:10, v/v, mobile phase B) containing 0.1% formic acid. The analysis was then performed by electrospray ionization in negative mode coupled with a triple quadrupole mass spectrometry, API 4000QT, monitoring two transitions for each analyte, one for the quantification and the other for confirmation. The method could be easily applied to the clinical practice thanks to the short run (7 min), the low amount of patient plasma necessary for the analysis (5 μL) and the fast sample processing based on protein precipitation. The method was therefore fully validated according to FDA and EMA guidelines. The linearity was assessed (R2≥0.998) over the concentration ranges of 50-8000 ng/mL for SORA and REGO, and 30-4000 ng/mL for their metabolites, that appropriately cover the therapeutic plasma concentrations. The presented method also showed adequate results in terms of intra- and inter-day accuracy and precision (CV ≤ 7.2% and accuracy between 89.4% and 108.8%), recovery (≥85.5%), sensitivity, analytes stability under various conditions and the absence of the matrix effect. Once the validation was successfully completed, the method was applied to perform the Cmin quantification of SORA, REGO and their metabolites in 54 plasma samples collected from patients enrolled in a clinical study ongoing at the National Cancer Institute of Aviano.