Dofetilide-d4
(Synonyms: 多非利特 D4; UK 68789 D4) 目录号 : GC47260
An internal standard for the quantification of dofetilide
Cas No.:1189700-56-8
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
Dofetilide-d4 is intended for use as an internal standard for the quantification of dofetilide by GC- or LC-MS. Dofetilide is a class III antiarrhythmic agent that prolongs cardiac action potential duration by selectively inhibiting the rapidly activating inward rectifying component of net delayed rectifier K+ current (IC50 = 31.5 nM in guinea pig cardiomyocytes).1 However, at 1 μM, dofetilide has pro-arrhythmic activity, inducing early afterdepolarizations (prolonged repolarization) in cell models and Torsade de Pointes in a rabbit screen for proarrhythmic properties when administered at a dose of 10 mg/kg.2 Formulations containing dofetilide have been used in the treatment of highly symptomatic atrial fibrillation and the conversion of flutter to normal sinus rhythm.3
1.Jurkiewicz, N.K., and Sanguinetti, M.C.Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agentCirculation Research72(1)75-83(1993) 2.Nalos, L., Varkevisser, R., Jonsson, M.K., et al.Comparison of the IKr blockers moxifloxacin, dofetilide and E-4031 in five screening models of pro-arrhythmia reveals lack of specificity of isolated cardiomyocytesBritish Journal of Pharmacology165(2)467-478(2012) 3.Dunnink, A., van Opstal, J.M., Oosterhoff, P., et al.Ventricular remodelling is a prerequisite for the induction of dofetilide-induced torsade de pointes arrhythmias in the anaesthetized, complete atrio-ventricular-block dogEuropace14(3)431-436(2012)
| Cas No. | 1189700-56-8 | SDF | |
| 别名 | 多非利特 D4; UK 68789 D4 | ||
| Canonical SMILES | CS(NC1=CC=C(OC([2H])([2H])C([2H])([2H])N(C)CCC2=CC=C(NS(C)(=O)=O)C=C2)C=C1)(=O)=O | ||
| 分子式 | C19H23D4N3O5S2 | 分子量 | 445.6 |
| 溶解度 | Chloroform: slightly soluble,Methanol: slightly soluble | 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2442 mL | 11.2208 mL | 22.4417 mL |
| 5 mM | 0.4488 mL | 2.2442 mL | 4.4883 mL |
| 10 mM | 0.2244 mL | 1.1221 mL | 2.2442 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。
Development and validation of a UPLC-MS/MS analytical method for dofetilide in mouse plasma and urine, and its application to pharmacokinetic study
J Pharm Biomed Anal 2019 Aug 5;172:183-188.PMID:31055183DOI:PMC6548664
A novel method using UPLC with tandem mass-spectrometric detection (UPLC-MS/MS) with positive electrospray ionization was developed for the detection of the antiarrhythmic drug, dofetilide, in mouse plasma and urine. Protein precipitation was performed on 10 μL of plasma and 2 μL of urine samples using Dofetilide-d4 as an internal standard, and separation of the analyte was accomplished on a C18 analytical column with the flow of 0.40 mL/min. Subsequently, the method was successfully applied to determine the pharmacokinetic parameters of dofetilide following oral and intravenous administration. The calibration curve was linear over the selected concentration range (R2 ≥ 0.99), with a lower limit of quantitation of 5 ng/mL. The intra-day and inter-day precisions, and accuracies obtained from a 5-day validation ranged from 3.00 to 7.10%, 3.80-7.20%, and 93.0-106% for plasma, and 3.50-9.00%, 3.70-10.0%, 87.0-106% for urine, while the recovery of dofetilide was 93.7% and 97.4% in plasma and urine, respectively. The observed pharmacokinetic profiles revealed that absorption is the rate-limiting step in dofetilide distribution and elimination. Pharmacokinetic studies illustrate that the absolute bioavailability of dofetilide in the FVB strain mice is 34.5%. The current developed method allows for accurate and precise quantification of dofetilide in micro-volumes of plasma and urine, and was found to be suitable for supporting in vivo pharmacokinetic studies.