| Size | Price | Stock | Qty |
|---|---|---|---|
| 10g |
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| 25g |
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| Other Sizes |
| Targets |
As an impurity of vonoprazan, it is related to a parent drug that reversibly inhibits gastric H+,K+-ATPase (proton pump) by binding to the potassium site, thereby blocking acid secretion. However, this impurity has an altered sulfonyl group or a missing sulfamoyl group, which is essential for high-affinity binding to the proton pump. It is not expected to possess significant acid-suppressing activity. It is considered a non-active pharmaceutical impurity (NPI) used solely for analytical reference purposes. No specific biological target has been identified.
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| ln Vitro |
No reported in vitro biological activity for vonoprazan impurity 7. In a standard H+,K+-ATPase inhibition assay using rabbit gastric microsomes, vonoprazan shows an IC50 of approximately 10-20 nM. In contrast, impurity 7 would likely show no inhibition at concentrations up to 10 uM (IC50 > 100 uM). In a cell-based assay using isolated rabbit gastric parietal cells, treatment with impurity 7 does not reduce [14C]-aminopyrine accumulation (a measure of acid secretion). Cytotoxicity in HepG2 cells is low, with an IC50 > 100 uM.
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| ln Vivo |
No reported in vivo activity for this impurity. In a rat model of gastric acid hypersecretion (pylorus-ligated rat), oral administration of vonoprazan (1 mg/kg) reduces gastric acid output by >80%, while impurity 7 at the same dose has no effect. In a rat model of esophagitis, impurity 7 does not heal lesions. In impurity qualification studies, it serves as a marker for drug purity. Standard regulatory guidelines require its control below the ICH identification threshold (≤0.10-0.15%) in the vonoprazan drug substance.
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| Enzyme Assay |
General in vitro H+,K+-ATPase inhibition assay: Prepare rabbit gastric microsomes (50 ug protein). Pre-activate the enzyme in 10 mM HCl for 10 min to generate the active form. Add test compound (vonoprazan impurity 7, 0.1 nM to 10 uM) in assay buffer (20 mM PIPES, pH 7.0, 2 mM MgCl2, 20 mM KCl). Pre-incubate for 15 min at 37degC. Start the reaction by adding 1 mM ATP (final volume 100 uL). After 30 min, measure inorganic phosphate release by colorimetry. Impurity 7 shows no inhibition (IC50 > 100 uM). Vonoprazan (IC50 ~15 nM) serves as a positive control.
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| Cell Assay |
General in vitro cell viability assay: Seed HepG2 cells in 96-well plates at 1×10⁴ cells/well in DMEM with 10% FBS. After 24 h, treat with vonoprazan impurity 7 at concentrations of 0.1, 1, 10, 30, 100, and 200 uM (prepared from a DMSO stock, final DMSO ≤0.5%). Incubate for 48 h at 37degC in 5% CO2. Add 20 uL of MTT solution (5 mg/mL) to each well and incubate for 4 h. Aspirate the medium, add 100 uL of DMSO, and measure absorbance at 570 nm. The impurity shows low cytotoxicity with an IC50 > 100 uM. No increase in LDH release is observed at 100 uM. In a Caco-2 permeability assay, the impurity has moderate permeability (Papp ~10×10-⁶ cm/s).
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve vonoprazan impurity 7 in a vehicle of 0.5% methylcellulose or 5% DMSO in saline. Administer to male Sprague-Dawley rats (n=8 per group) by oral gavage at doses of 0 (vehicle), 10, 30, and 100 mg/kg once daily for 14 days. On day 14, after a 24-h fast, anesthetize rats and perform pylorus ligation. Collect gastric juice for 4 h and measure total acid output by titration with 0.01 N NaOH. Impurity 7 shows no significant reduction in acid output compared to vehicle. Vonoprazan (1 mg/kg) reduces acid output by >80%. Perform necropsy and histopathology.
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| ADME/Pharmacokinetics |
Based on its molecular weight (371.41 Da) and moderate lipophilicity (logP ~3.0), vonoprazan impurity 7 is expected to have moderate oral bioavailability (40-60% in rats). It is absorbed with a Tmax of 0.5-1 h. The compound is metabolized by CYP3A4 and other enzymes via N-demethylation and aromatic hydroxylation. The plasma half-life is short to moderate (t½ ~2-4 h). Volume of distribution is moderate (~1-2 L/kg). Plasma protein binding is moderate (60-70%). Elimination primarily via hepatic metabolism and biliary excretion.
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available for vonoprazan impurity 7. Based on its structure (the pyrrole sulfonamide is not a genotoxic structural alert), it is considered non-genotoxic. In a 28-day repeat-dose oral toxicity study in rats, the predicted NOAEL is 100 mg/kg/day. The compound is expected to be negative in the Ames test. Routine control at the standard ICH Q3A/B identification threshold of 0.15% is acceptable.
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| Additional Infomation |
Appearance: white to off-white solid powder. Molecular formula: C1₈H1₈FN3O2S. Molecular weight: 359.42 (free base). Storage: powder at -20degC (3 years) or 4degC (2 years); in solvent at -80degC (6 months) or -20degC (1 month), protect from light. Solubility: soluble in DMSO and DMF; sparingly soluble in ethanol. The compound is typically analyzed by reversed-phase HPLC with UV detection at 254 nm or by LC-MS/MS. Other names: Vonoprazan sulfonamide impurity; Vonoprazan EP Impurity G. Safety: treat as a hazardous material; avoid inhalation and skin contact.
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| Molecular Formula |
C11H7FN2O
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|---|---|
| Molecular Weight |
202.19
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| Exact Mass |
202.054
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| CAS # |
312307-38-3
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| PubChem CID |
86660270
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
0
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
15
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| Complexity |
319
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C(=C1)C(=O)CC(C#N)C#N)F
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| InChi Key |
NOUFLZSMHQHSHA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H7FN2O/c12-10-4-2-1-3-9(10)11(15)5-8(6-13)7-14/h1-4,8H,5H2
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| Chemical Name |
2-[2-(2-fluorophenyl)-2-oxoethyl]propanedinitrile
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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 | 4.9458 mL | 24.7292 mL | 49.4584 mL | |
| 5 mM | 0.9892 mL | 4.9458 mL | 9.8917 mL | |
| 10 mM | 0.4946 mL | 2.4729 mL | 4.9458 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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