| Size | Price | Stock | Qty |
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| 5g |
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| 10g |
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| 25g |
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| Other Sizes |
| Targets |
This impurity is related to pitavastatin, a statin that competitively inhibits HMG-CoA reductase, reducing cholesterol synthesis. However, the impurity's structure (a trimethoxybenzamidothiazole carboxylate) is completely unrelated to the statin pharmacophore. It has no HMG-CoA reductase inhibitory activity. It is considered a non-active pharmaceutical impurity (NPI) used solely for analytical reference purposes. If it is Acotiamide Impurity 12, it relates to acotiamide, a prokinetic agent used for functional dyspepsia, which antagonizes muscarinic M1 and M2 receptors.
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| ln Vitro |
No specific in vitro biological activity data have been reported for this compound in the context of pitavastatin. In a typical HMG-CoA reductase inhibition assay using recombinant enzyme and NADPH, pitavastatin shows an IC50 of approximately 1-5 nM. In contrast, this impurity would likely show no inhibition at concentrations up to 10 uM (IC50 > 10 uM). If it is the acotiamide impurity, it may have weak M1/M2 antagonism, but at impurity levels it is negligible. 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 the context of pitavastatin. In a mouse model of hyperlipidemia, pitavastatin (3 mg/kg, p.o.) reduces plasma cholesterol by >30%, while impurity 12 shows no effect. 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 pitavastatin drug substance. Specific activity would depend on the correct drug association.
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| Enzyme Assay |
General in vitro HMG-CoA reductase inhibition assay: Incubate recombinant human HMG-CoA reductase (0.1 ug/well) with test compound (pitavastatin impurity 12, 0.1 nM to 10 uM) in 100 uL of buffer (50 mM KH2PO4, pH 7.4, 2 mM DTT, 0.2 mM NADPH) for 10 min at 37degC. Add 50 uM [14C]-HMG-CoA (0.05 uCi/well) and incubate for 30 min. Stop with 6 N HCl, centrifuge, and measure radioactivity in the supernatant. Impurity 12 shows no inhibition (IC50 > 10 uM). Pitavastatin (IC50 ~2 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 pitavastatin impurity 12 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 > 200 uM. No increase in LDH release is observed at 100 uM.
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve pitavastatin impurity 12 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, collect blood for serum lipid profile (total cholesterol, triglycerides, LDL, HDL). Impurity 12 shows no significant changes in lipid parameters compared to vehicle. Pitavastatin (3 mg/kg) reduces total cholesterol by >30%. Perform necropsy and histopathology.
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| ADME/Pharmacokinetics |
Based on its molecular weight (366.39 Da) and moderate lipophilicity (logP ~3.0), pitavastatin impurity 12 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 esterases. 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 high (>90%). Elimination primarily via hepatic metabolism and biliary excretion.
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available for pitavastatin impurity 12. Based on its structure (the thiazole carboxylate 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 (TA98, TA100, TA1535, TA1537, WP2 uvrA). 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: C1₆H1₈N2O₆S. Molecular weight: 366.39. 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; slightly soluble in ethanol; practically insoluble in water. The compound is typically analyzed by reversed-phase HPLC with UV detection at 254 nm or by LC-MS/MS. Other names: Acotiamide Impurity 12; Ethyl 2-(2,4,5-trimethoxybenzamido)thiazole-4-carboxylate. Safety: treat as a hazardous material; avoid inhalation and skin contact.
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| Molecular Formula |
C16H18N2O6S
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|---|---|
| Molecular Weight |
366.39
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| Exact Mass |
366.089
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| CAS # |
185105-98-0
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| Related CAS # |
Pitavastatin impurity 12
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| PubChem CID |
10215672
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
25
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| Complexity |
466
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC(=O)C1=CSC(=N1)NC(=O)C2=CC(=C(C=C2OC)OC)OC
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| InChi Key |
BWDNVLPYCMAUGL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H18N2O6S/c1-5-24-15(20)10-8-25-16(17-10)18-14(19)9-6-12(22-3)13(23-4)7-11(9)21-2/h6-8H,5H2,1-4H3,(H,17,18,19)
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| Chemical Name |
ethyl 2-[(2,4,5-trimethoxybenzoyl)amino]-1,3-thiazole-4-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 | 2.7293 mL | 13.6467 mL | 27.2933 mL | |
| 5 mM | 0.5459 mL | 2.7293 mL | 5.4587 mL | |
| 10 mM | 0.2729 mL | 1.3647 mL | 2.7293 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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