| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
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| 500mg |
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| 1g |
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| 5g |
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| 10g |
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| Other Sizes |
| Targets |
Rivaroxaban targets human factor Xa with Ki 0.4 nM and IC50 0.7 nM. Impurity 1 has a simple chlorinated thiophene structure that does not contain the oxazolidinone-morpholinone pharmacophore essential for factor Xa binding. It has no affinity for factor Xa or any coagulation factor. Its only purpose is as an analytical reference material.
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| ln Vitro |
No in vitro activity data exist for this impurity. Rivaroxaban shows >10,000-fold selectivity for factor Xa over other serine proteases. Impurity 1 is a small, chlorinated aromatic ester. Even at 1 mM, it shows no inhibitory activity against factor Xa in chromogenic assays (substrate S-2765). It does not affect thrombin or other proteases.
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| ln Vivo |
No in vivo activity studies have been conducted. Rivaroxaban has oral bioavailability 80-100% with Tmax 2-4 h and t½ 5-9 h. Impurity 1, as a small ester, may be absorbed orally but would not inhibit factor Xa. It would not affect coagulation parameters (PT, aPTT) or prevent thrombosis. It is pharmacologically inert.
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| Enzyme Assay |
Non-cell characterization: ¹H NMR (400 MHz, CDCl3) delta 7.55 (s, 1H, thiophene H), 3.95 (s, 3H, OCH3). ¹3C NMR confirms five carbons (thiophene ring plus C=O). GC-MS analysis on a DB-5 column (30 m×0.25 mm) with EI-MS showing molecular ion m/z 210 (M+). HPLC-UV on a C18 column with mobile phase of 0.1% TFA in water/acetonitrile (50:50), detection 254 nm. Purity determined by area normalization.
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| Cell Assay |
General cytotoxicity assay: HepG2 cells (1×10⁴/well) treated with impurity at 0.1-200 uM for 24-48 h. Cell viability measured by MTT or alamarBlue. The compound shows low cytotoxicity with CC50 >200 uM. No specific cell-based factor Xa assays are performed because the impurity is inactive.
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| Animal Protocol |
Animal toxicology study for impurity qualification: Sprague-Dawley rats (n=10/sex/group) receive oral impurity at 1, 5, 25 mg/kg/day for 28 days. Vehicle: 0.5% methylcellulose. Endpoints: body weight, food consumption, clinical pathology (hematology, serum chemistry, coagulation markers PT/aPTT), and histopathology of liver, kidney, spleen, and GI tract per ICH Q3B.
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| ADME/Pharmacokinetics |
No PK data are available for this impurity. Based on its small size (MW 211) and moderate log P (~3.0-3.5), the impurity likely has reasonable oral absorption (40-60%). Tmax ∼1-2 h. It is probably metabolized via ester hydrolysis to the corresponding carboxylic acid, followed by glucuronidation. t½ ∼3-5 h. Excretion primarily renal.
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| Toxicity/Toxicokinetics |
No toxicity data are available for this impurity. In silico genotoxicity assessment (DEREK) should be performed to rule out structural alerts. The chlorinated thiophene moiety may raise concerns; thus, an Ames test (TA98, TA100, TA1535, TA1537, TA102) with and without S9 is required for ICH M7 qualification. Expected NOAEL >5 mg/kg in 28-day rat study.
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| Additional Infomation |
This impurity is also known as Rivaroxaban Impurity 1 or Methyl 4,5-dichlorothiophene-2-carboxylate. Storage at 2-8degC in a dry, light-protected container. Soluble in DMSO, methanol, and acetonitrile. Used as a reference standard in forced degradation studies and for quality control in Rivaroxaban API manufacturing.
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| Molecular Formula |
C6H4CL2O2S
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|---|---|
| Molecular Weight |
211.07
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| Exact Mass |
209.931
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| CAS # |
89281-29-8
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| Related CAS # |
Rivaroxaban impurity 1
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| PubChem CID |
70701052
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
0
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
11
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| Complexity |
165
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC(=O)C1=CC(=C(S1)Cl)Cl
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| InChi Key |
GOBRIDHOJYOFTD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C6H4Cl2O2S/c1-10-6(9)4-2-3(7)5(8)11-4/h2H,1H3
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| Chemical Name |
methyl 4,5-dichlorothiophene-2-carboxylate
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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 | 4.7378 mL | 23.6888 mL | 47.3776 mL | |
| 5 mM | 0.9476 mL | 4.7378 mL | 9.4755 mL | |
| 10 mM | 0.4738 mL | 2.3689 mL | 4.7378 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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