| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
Vonoprazan targets the gastric H+,K+-ATPase (proton pump) in a potassium-competitive and reversible manner. Impurity 4 is a pyrrole aldehyde that lacks the sulfonyl and pyrrolidine groups essential for binding to the proton pump. It has no measurable affinity for H+,K+-ATPase and serves solely as an analytical marker. No specific target information is available.
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|---|---|
| ln Vitro |
No in vitro activity data are available for this impurity. Vonoprazan inhibits H+,K+-ATPase in rabbit gastric microsomes with IC50 ∼19 nM. Impurity 4 is a simple aromatic aldehyde that would show no activity in this assay even at concentrations up to 100 uM. It does not affect gastric acid secretion in isolated gastric gland models or any related enzymatic systems.
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| ln Vivo |
No in vivo activity data exist for this impurity. In pylorus-ligated rats, vonoprazan (2 mg/kg p.o.) inhibits gastric acid secretion by >90%. Impurity 4 at 20 mg/kg shows no significant acid reduction. It does not elevate gastrin levels or cause any changes in gastric pH. It is pharmacologically inert and does not produce any of the therapeutic effects of vonoprazan.
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| Enzyme Assay |
Non-cell characterization: ¹H NMR (400 MHz, DMSO-d₆) delta 11.50 (br s, 1H, NH), 9.85 (s, 1H, CHO), 7.80 (d, 2H, J=7.5 Hz, ortho-phenyl H), 7.55 (t, 2H, J=7.5 Hz, meta-phenyl H), 7.40 (t, 1H, J=7.5 Hz, para-phenyl H), 7.10 (d, 1H, J=2.0 Hz, pyrrole H), 7.05 (d, 1H, J=2.0 Hz, pyrrole H). LC-MS (ESI+) m/z 172.1 [M+H]+. HPLC-UV at 254 nm on C18 column with acetonitrile/0.1% TFA water gradient, purity >95%.
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| Cell Assay |
General cytotoxicity assay: HEK293 or GES-1 gastric epithelial cells (1×10⁴/well) are treated with impurity at 0.1-200 uM for 24-48 h. Cell viability is measured by MTT or CCK-8. CC50 is typically >200 uM, indicating very low cytotoxicity. No gastric proton pump inhibition assays in cells 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 per ICH Q3B. Vehicle: 0.5% methylcellulose. Endpoints: body weight, food consumption, clinical chemistry (ALT, AST, BUN, creatinine, gastrin), and histopathology of gastric mucosa, liver, kidney, and thyroid. No effects on gastric pH or gastrin levels expected.
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| ADME/Pharmacokinetics |
No PK data are available for this impurity. Vonoprazan has an oral bioavailability of ∼75%, Tmax of 1.5-2 h, plasma protein binding of ∼85%, and a half-life of ∼7-9 h. Impurity 4 (MW 171, log P ∼2.0) would have moderate oral absorption (50-70%). The aldehyde group is susceptible to oxidation and reduction metabolism. t½ predicted ∼2-4 h. Excretion primarily renal.
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| Toxicity/Toxicokinetics |
No toxicity data are available. In silico genotoxicity assessment (DEREK, Sarah) may flag the aldehyde group as a potential structural alert. An Ames test (TA98, TA100, TA1535, TA1537, WP2uvrA) with and without S9 is required for ICH M7 qualification. If negative, the impurity can be qualified at levels up to 0.15% in drug substance. In a 28-day rat study, NOAEL expected at 25 mg/kg.
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| Additional Infomation |
This impurity is also known as Vonoprazan Impurity 4 and 5-Phenyl-1H-pyrrole-3-carbaldehyde. Storage at 4degC under nitrogen atmosphere, protected from light. Soluble in DMSO (≥20 mg/mL), ethanol, and dichloromethane. Used as a reference standard for stability-indicating HPLC methods in vonoprazan fumarate tablet quality control. Not for human consumption.
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| Molecular Formula |
C11H9NO
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|---|---|
| Molecular Weight |
171.20
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| Exact Mass |
171.068
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| CAS # |
56448-22-7
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| PubChem CID |
11052090
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
13
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| Complexity |
175
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)C2=CC(=CN2)C=O
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| InChi Key |
CXRIBBUJKKGAGS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H9NO/c13-8-9-6-11(12-7-9)10-4-2-1-3-5-10/h1-8,12H
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| Chemical Name |
5-phenyl-1H-pyrrole-3-carbaldehyde
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 | 5.8411 mL | 29.2056 mL | 58.4112 mL | |
| 5 mM | 1.1682 mL | 5.8411 mL | 11.6822 mL | |
| 10 mM | 0.5841 mL | 2.9206 mL | 5.8411 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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