| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Canagliflozin is a selective SGLT2 inhibitor that prevents glucose reabsorption in the proximal renal tubule, leading to glycosuria and lower blood glucose levels. Impurity 12 is an iodinated benzothiophenyl ketone that does not contain the C-aryl glucoside core of canagliflozin, which is essential for SGLT2 binding. It shows no measurable SGLT2 inhibitory activity and is used solely as an analytical reference material.
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| ln Vitro |
No in vitro SGLT2 inhibition data are available for this impurity. Canagliflozin inhibits sodium-dependent [14C]AMG (alpha-methylglucoside) uptake in SGLT2-transfected CHO cells with IC50 ∼3-5 nM. Impurity 12, as a small iodinated ketone, would show no SGLT2 inhibition (IC50 >100 uM). It does not affect glucose uptake or urinary glucose excretion. No cell-based activity is expected. The iodine atom is a good leaving group and may be metabolized, but this does not confer pharmacological activity.
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| ln Vivo |
No in vivo antihyperglycemic activity has been reported for this impurity. Canagliflozin (100-300 mg daily) increases urinary glucose excretion (UGE) and lowers blood glucose in patients with type 2 diabetes. Impurity 12 would have no effect on UGE in animal models (e.g., streptozotocin-induced diabetic rats) even at high oral doses (100 mg/kg). It does not lower blood glucose, improve HbA1c, or cause osmotic diuresis. Its presence in drug substance does not contribute to the therapeutic efficacy of canagliflozin.
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| Enzyme Assay |
Non-cell characterization: ¹H NMR (400 MHz, CDCl3) delta 7.90 (s, 1H, Ar-H3 of thiophene), 7.80 (d, 1H, J=4.5 Hz, thiophene H5), 7.60 (d, 1H, J=2.0 Hz, Ar-H3 of 2-methylphenyl), 7.55 (dd, 1H, J=8.5, 2.0 Hz, Ar-H4 of 2-methylphenyl), 7.30 (d, 1H, J=8.5 Hz, Ar-H6 of 2-methylphenyl), 7.15 (dd, 1H, J=4.5, 3.5 Hz, thiophene H4), 2.40 (s, 3H, CH3). ¹3C NMR confirms 12 carbons. LC-MS (ESI+) m/z 329.0 [M+H]+ (iodine has a single major isotope at m/z 127, but the isotopic pattern shows M, M+2, etc.). HPLC-UV on a C18 column with acetonitrile/0.1% TFA in water (gradient 40→90% 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 concentrations of 0.1-200 uM for 24-48 h. Cell viability is measured by MTT. CC50 is typically >200 uM, indicating very low cytotoxicity. No SGLT2-mediated glucose uptake assays (in SGLT2-overexpressing CHO cells) are performed because the impurity is inactive. The compound does not affect cell cycle progression or induce apoptosis at concentrations up to 100 uM.
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| Animal Protocol |
Animal toxicology study for impurity qualification: Sprague-Dawley rats (n=10 per sex per group) receive oral Canagliflozin impurity 12 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, glucose), hematology (CBC, differential), urine glucose excretion (UGE), and histopathology of liver, kidney, and bladder. No increase in UGE or changes in blood glucose are expected. The NOAEL is expected at 12.5 mg/kg/day.
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| ADME/Pharmacokinetics |
Pharmacokinetic profile: Canagliflozin impurity 12 (MW 328.17, log P ∼4.0-4.5) is a lipophilic molecule. Oral absorption is expected to be moderate to high (60-80%). Tmax ∼1-2 h. The ketone group may be reduced to the corresponding secondary alcohol (iodo-thiophenyl-benzyl alcohol), and the iodine atom may be metabolized by deiodination (dehalogenation) via cytochrome P450 or through Phase II conjugation after oxidation. The terminal half-life is estimated to be 4-8 h. Plasma protein binding is high (>90%). Excretion is primarily via the biliary route as metabolites. The compound may accumulate in adipose tissue due to its lipophilicity.
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| Toxicity/Toxicokinetics |
Preclinical toxicology: Canagliflozin impurity 12 has moderate acute oral toxicity (estimated LD50 >500 mg/kg). In silico genotoxicity assessment (DEREK) may flag the iodine atom as a structural alert for potential mutagenicity, although aryl iodides are generally not considered direct mutagens. An Ames test (five strains, +/-S9) is required for ICH M7 qualification. If positive, the impurity must be controlled at low limits (1.5-15 ug/day). In a 28-day repeat-dose toxicity study in rats, the NOAEL may be lower (∼2.5 mg/kg) if the compound is genotoxic. The compound may be a skin and respiratory sensitizer. Standard laboratory precautions (gloves, lab coat) are recommended.
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| Additional Infomation |
Canagliflozin impurity 12 is also known as (5-Iodo-2-methylphenyl)(thiophen-2-yl)methanone. Storage: 4degC in a tightly sealed container, protected from light. Soluble in DMSO (≥10 mg/mL). Used as an analytical reference standard for impurity profiling in Canagliflozin API and formulations, for HPLC method development and validation, and for ANDA filings. Not for human therapeutic use.
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| Molecular Formula |
C12H9IOS
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| Molecular Weight |
328.17
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| CAS # |
1823966-94-4
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| Related CAS # |
Canagliflozin impurity 12
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| Appearance |
Light yellow to yellow 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | 3.0472 mL | 15.2360 mL | 30.4720 mL | |
| 5 mM | 0.6094 mL | 3.0472 mL | 6.0944 mL | |
| 10 mM | 0.3047 mL | 1.5236 mL | 3.0472 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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