Afatinib-d6
(Synonyms: BIBW 2992 D6) 目录号 : GC46809
An internal standard for the quantification of afatinib
Cas No.:1313874-96-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Afatinib-d6 is intended for use as an internal standard for the quantification of afatinib by GC- or LC-MS. Afatinib is an irreversible inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 (IC50s = 0.5 and 14 nM, respectively).1 It increases the cytotoxicity of adriamycin in a concentration-dependent manner in multidrug-resistant A549T lung cancer cells overexpressing P-glycoprotein.2 Afatinib (20 mg/kg) reduces tumor growth in ErbB2-amplified NCI-N87 and NUGC4 gastric cancer mouse xenograft models.3 Formulations containing afatinib have been used in the treatment of non-small cell lung cancer.
1.Eskens, F.A.L.M., Mom, C.H., Planting, A.S.T., et al.A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumoursBr. J. Cancer98(1)80-85(2008) 2.Zhang, Y., Wang, C.-Y., Duan, Y.-J., et al.Afatinib decreases P-glycoprotein expression to promote adriamycin toxicity of A549T cellsJ. Cell. Biochem.119(1)414-423(2018) 3.Yoshioka, T., Shien, K., Namba, K., et al.Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancerCancer Sci.109(4)1166-1176(2018)
| Cas No. | 1313874-96-2 | SDF | |
| 别名 | BIBW 2992 D6 | ||
| Canonical SMILES | FC(C=C1)=C(Cl)C=C1NC2=NC=NC3=C2C=C(NC(/C=C/CN(C([2H])([2H])[2H])C([2H])([2H])[2H])=O)C(O[C@@H]4COCC4)=C3 | ||
| 分子式 | C24H19ClD6FN5O3 | 分子量 | 492 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 30 mg/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 | 2.0325 mL | 10.1626 mL | 20.3252 mL |
| 5 mM | 0.4065 mL | 2.0325 mL | 4.065 mL |
| 10 mM | 0.2033 mL | 1.0163 mL | 2.0325 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。
Quantification of afatinib, alectinib, crizotinib and osimertinib in human plasma by liquid chromatography/triple-quadrupole mass spectrometry; focusing on the stability of osimertinib
J Chromatogr B Analyt Technol Biomed Life Sci 2019 Apr 15;1113:37-44.PMID:30889498DOI:10.1016/j.jchromb.2019.03.011.
The development and full validation of a sensitive and selective ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method are described for the simultaneous analysis of afatinib, alectinib, crizotinib and osimertinib in human lithium heparinized plasma. Afatinib-d6, crizotinib-d5 and erlotinib-d6 were used as internal standards. Given osimertinib's instability in plasma and whole blood at ambient temperature, samples should be solely processed on ice (T = 0 °C). Chromatographic separation was obtained on an Acquity UPLC ® BEH C18; 2.1 × 50 mm, 1.7 μm column, which was eluted with 0.400 mL/minute flow on a linear gradient, consisting of 10 mM ammonium formate (pH 4.5) and acetonitrile. Calibration curves for all compounds were linear for concentration ranges of 1.00 to 100 ng/mL for afatinib and 10.0 to 1000 ng/mL for alectinib, crizotinib and osimertinib, herewith validating the lower limits of quantification at 1.00 ng/mL for afatinib and 10.0 ng/mL for alectinib, crizotinib and osimertinib. Within-run and between-run precision measurements fell within 10.2%, with accuracy ranging from 89.2 to 110%.
Pharmacokinetic Study and Tissue Distribution of Lorlatinib in Mouse Serum and Tissue Samples by Liquid Chromatography-Mass Spectrometry
J Anal Methods Chem 2019 Mar 4;2019:7574369.PMID:30949374DOI:10.1155/2019/7574369.
In the present study, we developed and validated a rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of lorlatinib in mouse serum and tissue samples, and such a method was successfully applied to investigate the pharmacokinetic study and tissue distribution of lorlatinib after oral administration. Samples were processed with methanol to precipitate protein and extract drugs, and Afatinib-d6 was used as the internal standard (IS). For LC-MS/MS analysis, compounds were separated on a C18 column by gradient elution (0.1% of formic acid and methanol) at 0.5 mL/min in the positive-ion mode with m/z 407.28 [M + H]+ for lorlatinib and m/z 492.10 [M + H]+ for IS. Good linearity was observed within the calibration ranges. Selectivity, accuracy (-6.42% to 8.84%), precision (1.69% to 10.98%), recoveries (91.4% to 115.0%), and matrix effect (84.2% to 110.6%) were all within the acceptable ranges. After oral administration, serum concentration of lorlatinib quickly achieved the maximal concentration (2,705.683 ± 539.779 μg/L) at 0.625 ± 0.231 h. The highest concentration was detected in the liver (3,153.93 ng/100 mg), followed by the stomach (2,159.92 ng/100 mg) and the kidney (548.83 ng/100 mg). In conclusion, a simple and rapid detection method was established and validated for determination of lorlatinib in blood and tissue samples of mouse. The pharmacokinetic study and tissue distribution of lorlatinib were successfully investigated using this method.