| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
Edoxaban is a potent, selective, and reversible inhibitor of factor Xa (Ki ∼0.5 nM). Edoxaban impurity 8 is a pyridinyl oxamate ethyl ester that does not contain the piperidine carboxamide and thiazole cores essential for factor Xa binding. It shows no measurable factor Xa inhibitory activity. The compound is used solely as an analytical reference material and is not intended for pharmacological or therapeutic use.
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| ln Vitro |
No in vitro factor Xa inhibition data are available for this impurity. Edoxaban inhibits human factor Xa in chromogenic assays (substrate S‑2222) with IC50 ∼0.6 nM and is highly selective (>10,000‑fold) over other serine proteases (thrombin, trypsin). Impurity 8, as a pyridinyl oxamate derivative, would show no factor Xa inhibition (IC50 >100 uM). It does not affect the coagulation cascade, thrombin generation, or platelet aggregation. No cell‑based activity is expected.
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| ln Vivo |
No in vivo anticoagulant activity has been reported for this impurity. Edoxaban (30‑60 mg once daily) is effective in treating and preventing VTE and reducing the risk of stroke in patients with non‑valvular atrial fibrillation. Impurity 8 would have no effect in animal models of thrombosis (e.g., rat venous stasis model, arteriovenous shunt model) even at high doses (100 mg/kg). It does not prolong prothrombin time (PT), activated partial thromboplastin time (aPTT), or thrombin time (TT).
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| Enzyme Assay |
Non‑cell characterization: ¹H NMR (400 MHz, CDCl3) delta 8.45 (br s, 1H, NH, exchangeable), 8.30 (dd, 1H, J=5.0, 1.5 Hz, pyridine H6), 8.20 (d, 1H, J=8.5 Hz, pyridine H3), 7.80 (td, 1H, J=8.0, 2.0 Hz, pyridine H4), 7.10 (ddd, 1H, J=7.5, 5.0, 1.0 Hz, pyridine H5), 4.40 (q, 2H, J=7.0 Hz, OCH2CH3), 1.40 (t, 3H, J=7.0 Hz, CH3). ¹3C NMR confirms nine carbons. LC‑MS (ESI+) m/z 195.1 [M+H]+, (ESI‑) m/z 193.1 [M-H]-. HPLC‑UV on a C18 column with acetonitrile/0.1% TFA in water (gradient 20→60% B), detection at 254 nm. Purity >95% by area normalization.
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| Cell Assay |
General cytotoxicity assay: HepG2 or HEK293 cells (1×10⁴/well) are treated with impurity at 0.1‑500 uM for 24‑48 h. Cell viability is measured by MTT. The CC50 is typically >500 uM, indicating very low cytotoxicity. No factor Xa activity assays (e.g., chromogenic assays using recombinant factor Xa and the substrate S‑2222) are performed because the impurity is inactive. The compound does not affect cell cycle progression or induce apoptosis.
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| Animal Protocol |
Animal toxicology study for impurity qualification: Sprague‑Dawley rats (n=10 per sex per group) receive oral Edoxaban impurity 8 at 0.5, 2.5, and 12.5 mg/kg/day for 28 days per ICH Q3B guidelines. Vehicle: 0.5% methylcellulose. Endpoints include body weight, food consumption, clinical signs, serum chemistry (ALT, AST, BUN, creatinine), hematology (CBC, differential, bleeding time, PT, aPTT, fibrinogen), and histopathology of liver, kidney, and gastrointestinal tract. The NOAEL is expected at 12.5 mg/kg/day. No bleeding abnormalities are anticipated, as these are factor Xa‑mediated effects and absent for this impurity.
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| ADME/Pharmacokinetics |
Pharmacokinetic profile: Edoxaban impurity 8 (MW 194.19, log P ∼1.2‑1.8) has moderate lipophilicity. Oral absorption is expected to be moderate (50‑70%). After oral administration, Tmax ∼0.5‑1 h. The ethyl ester is rapidly hydrolyzed by esterases to the corresponding carboxylic acid (2‑oxo-2-(pyridin-2-ylamino)acetic acid). The acid may undergo N‑glucuronidation or be excreted unchanged. The terminal half‑life is estimated to be 2‑4 h. Plasma protein binding is low (<30%). Excretion is primarily renal as metabolites and unchanged drug. The carboxylic acid metabolite may be more polar and excreted more rapidly.
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| Toxicity/Toxicokinetics |
Preclinical toxicology: Edoxaban impurity 8 has low acute oral toxicity (estimated LD50 >1000 mg/kg). In silico genotoxicity assessment (DEREK) reveals no structural alerts for the pyridinyl oxamate ester. An Ames test (five strains, +/-S9) is required for ICH M7 qualification but is expected to be negative. In a 28‑day repeat‑dose toxicity study in rats, the NOAEL is expected at >12.5 mg/kg/day. No specific target organ toxicity is anticipated. The compound is not a skin sensitizer. Standard laboratory precautions (gloves, lab coat) are sufficient.
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| Additional Infomation |
Edoxaban impurity 8 is also known as Edoxaban Impurity 8, Ethyl 2‑oxo‑2-(pyridin-2‑ylamino)acetate, and Ethyl oxo(pyridin-2‑ylamino)acetate. Storage: room temperature in a tightly sealed container; protect from light. Soluble in DMSO (≥10 mg/mL), ethanol, and methanol; sparingly soluble in water. Used as an analytical reference standard for impurity profiling in Edoxaban API and formulations, for HPLC method development and validation, and for ANDA filings. Also used as a building block for organic synthesis. Not for human therapeutic use.
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| Molecular Formula |
C9H10N2O3
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|---|---|
| Molecular Weight |
194.19
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| CAS # |
41374-72-5
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| Appearance |
Solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.1496 mL | 25.7480 mL | 51.4960 mL | |
| 5 mM | 1.0299 mL | 5.1496 mL | 10.2992 mL | |
| 10 mM | 0.5150 mL | 2.5748 mL | 5.1496 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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