| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
As an impurity of olmesartan medoxomil, trityl olmesartan medoxomil impurity III itself has no direct pharmacological target. This compound contains an N-trityl-protected tetrazole ring and is a byproduct of the synthesis of the key intermediate N-tritylolmesartan medoxomil. In olmesartan medoxomil synthesis, the trityl protecting group on the tetrazole ring is subsequently removed during basic hydrolysis to generate the active olmesartan. Impurity III retains the intact trityl protecting group and is a process-related impurity resulting from incomplete deprotection or improper reaction conditions.
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|---|---|
| ln Vitro |
As a synthetic byproduct rather than an active pharmaceutical ingredient, this impurity has no research value for in vitro pharmacological activity. In pharmaceutical quality standards, process-related impurities of this type are typically controlled at levels not exceeding 0.1%, at which concentration they make no contribution to the overall pharmacological effect of the drug product. The pharmacological significance of this impurity is limited to ensuring the purity of the active pharmaceutical ingredient.
|
| ln Vivo |
At clinical doses of the drug product, it is present only in trace amounts (typically below 0.1%) and contributes nothing to the antihypertensive effect. The primary concern associated with such impurities lies in potential toxicological effects rather than pharmacological activity.
|
| Enzyme Assay |
It can be analyzed by high-performance liquid chromatography (HPLC) for pharmaceutical quality control purposes. Typical chromatographic conditions involve a C18 reversed-phase column (e.g., Poroshell HPH-C18, 150 × 4.6 mm, 2.7 μm) with gradient elution using 0.1% formic acid in water as mobile phase A and 0.1% formic acid in methanol as mobile phase B at a flow rate of 0.5 mL/min over a total runtime of approximately 20 minutes, with detection by UV absorbance at 254 nm. The impurity reference standard is used for qualitative and quantitative analysis to ensure that its content in the drug substance is controlled within acceptable limits.
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| Cell Assay |
If cytotoxicity evaluation is required, general impurity toxicity screening methods may be used: human hepatocytes (e.g., HepG2 cells) are seeded into 96-well plates at densities of 5×10³-1×10⁴ cells/well, cultured overnight, then treated with various concentrations of the impurity (0.1-100 μM) for 24-72 hours, with cell viability assessed by MTT or CCK-8 assays. Such methods are used only for safety assessment, not pharmacodynamic studies.
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| Animal Protocol |
In API quality control studies, the toxicological and pharmacological evaluation of impurities is typically conducted through quantitative analysis using reference standards and impurity profiling, rather than direct animal studies. In silico predictions for genotoxic risk may be performed according to GMP guidelines.
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| ADME/Pharmacokinetics |
This impurity is a byproduct that requires removal during the synthetic process. For the active ingredient olmesartan medoxomil, following oral administration, it is rapidly hydrolyzed by esterases in the gastrointestinal tract to the active metabolite olmesartan, which has a half-life of 10-15 hours, a bioavailability of approximately 26%, with about 40% excreted renally and the remainder excreted in feces.
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| Toxicity/Toxicokinetics |
As a process-related impurity in pharmaceuticals, its control limit is based on ICH Q3A guidelines, which stipulate that impurities present at levels not exceeding 0.1% do not require individual toxicological identification. If levels exceed this threshold, toxicological evaluation is required. It should be noted that nitrosamine impurities have been a significant safety concern for sartan drugs; however, these belong to the category of "genotoxic impurities" and are distinct from the structurally related impurities described herein. This compound is intended for scientific research use and is not for human therapeutic applications.
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| References |
[1]. Development of efficient one-pot three-component assembly of trityl olmesartan medoxomil. Bioorg Med Chem. 2018 Aug 7;26(14):4348-4359.
|
| Molecular Formula |
C48H42N6O5
|
|---|---|
| Molecular Weight |
782.88
|
| Exact Mass |
782.322
|
| CAS # |
1227626-51-8
|
| PubChem CID |
57758773
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
9.289
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
15
|
| Heavy Atom Count |
59
|
| Complexity |
1420
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C(=C)(C)C1N=C(CCC)N(CC2=CC=C(C3=CC=CC=C3C3N(C(C4=CC=CC=C4)(C4=CC=CC=C4)C4=CC=CC=C4)N=NN=3)C=C2)C=1C(OCC1=C(C)OC(=O)O1)=O
|
| InChi Key |
YQJFAQFEAOEJFL-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C48H42N6O5/c1-5-17-42-49-43(32(2)3)44(46(55)57-31-41-33(4)58-47(56)59-41)53(42)30-34-26-28-35(29-27-34)39-24-15-16-25-40(39)45-50-51-52-54(45)48(36-18-9-6-10-19-36,37-20-11-7-12-21-37)38-22-13-8-14-23-38/h6-16,18-29H,2,5,17,30-31H2,1,3-4H3
|
| Chemical Name |
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 5-prop-1-en-2-yl-2-propyl-3-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylate
|
| Synonyms |
Trityl olmesartan medoxomil impurity III; 1227626-51-8; (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 5-prop-1-en-2-yl-2-propyl-3-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylate; (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-(prop-1-en-2-yl)-2-propyl-1-((2'-(1-trityl-1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylate; Olmesartan Impurity 40;
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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 | 1.2773 mL | 6.3867 mL | 12.7733 mL | |
| 5 mM | 0.2555 mL | 1.2773 mL | 2.5547 mL | |
| 10 mM | 0.1277 mL | 0.6387 mL | 1.2773 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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