| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
As an impurity of olmesartan medoxomil, impurity C itself is not designed as an active pharmaceutical ingredient; therefore, its direct pharmacological target has not been systematically studied. The parent compound olmesartan medoxomil is a selective angiotensin AT1 receptor antagonist with an IC₅₀ of 66.2 μM. Olmesartan medoxomil is rapidly hydrolyzed in vivo to the active metabolite olmesartan, which exerts its antihypertensive effect by selectively blocking angiotensin II binding to AT1 receptors. Impurity C retains the core structure of olmesartan medoxomil but has a propenyl group at the C4 position instead of the hydroxyisopropyl group, while retaining both protecting groups (the tetrazole ring and dioxoleneone structure). This structural difference may affect its ability to bind AT1 receptors and its in vivo conversion characteristics.
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|---|---|
| ln Vitro |
This compound is defined as a pharmaceutical impurity, and its quality control significance lies in ensuring the purity of the active pharmaceutical ingredient, rather than serving as an independent pharmacological tool for research. Impurity C differs structurally from olmesartan medoxomil primarily in the C4 side chain, which is a propenyl group (-C(CH₃)=CH₂) instead of a 2-hydroxyisopropyl group (-C(OH)(CH₃)₂). This difference may affect the compound's AT1 receptor affinity, plasma protein binding, and metabolic stability. In drug quality studies, impurity C is typically used as a reference standard for qualitative and quantitative analysis by HPLC to ensure that the content of this impurity in the drug substance is controlled within acceptable limits.
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| ln Vivo |
As a pharmaceutical impurity, this compound typically exists only in trace amounts (typically <0.1%) in the drug substance and finished product, so its pharmacological contribution in vivo is negligible. The parent compound olmesartan medoxomil is rapidly hydrolyzed in vivo by esterases to the active metabolite olmesartan, which exerts its antihypertensive effect by blocking angiotensin II binding to AT1 receptors. Following oral administration, peak plasma concentrations of olmesartan occur 1-3 hours after administration, with an elimination half-life of 10-15 hours. If present in trace amounts in the formulation, impurity C may behave similarly to olmesartan medoxomil in vivo, but its hydrolysis rate and AT1 receptor binding activity may be altered due to the structural difference at the C4 position.
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| Enzyme Assay |
The AT1 receptor binding protocol for olmesartan medoxomil impurity C as a reference standard can follow the method for the parent compound. A typical AT1 receptor radioligand binding assay uses membranes from cells overexpressing the angiotensin II AT1 receptor (e.g., CHO cells expressing human AT1 receptors). Membrane proteins are incubated with [¹²⁵I]- or [³H]-labeled angiotensin II tracer and various concentrations of impurity C or olmesartan medoxomil (0.1 nM-100 μM). Following incubation at room temperature for 60-120 minutes, the reaction is terminated by rapid vacuum filtration, and filters are washed to remove unbound tracer. After drying, retained radioactivity on filters is measured using a gamma counter or liquid scintillation counter to calculate specific binding inhibition rates. Olmesartan medoxomil has an IC₅₀ of 66.2 μM in this assay system.
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| Cell Assay |
As a pharmaceutical impurity, its cytotoxicity evaluation can use standard MTT or CCK-8 assays. The typical protocol is as follows: Human hepatocyte cells (e.g., HepG2 cells) or human renal epithelial cells (e.g., HEK293 cells) are seeded into 96-well culture plates at densities of 5×10³-1×10⁴ cells/well in medium containing 10% fetal bovine serum and cultured overnight. The following day, various concentrations of impurity C (0.1-100 μM) are added and incubated for 24-72 hours. Cell viability is assessed using MTT assays, with absorbance measured at 570 nm. Olmesartan medoxomil is included as a control. For mechanistic studies, changes in signaling pathway proteins (such as AT1 receptor, ERK1/2, etc.) can be detected by Western blot.
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| Animal Protocol |
As a pharmaceutical impurity, separate animal studies for this compound are generally not required. For related research, the in vivo evaluation protocol for olmesartan medoxomil can be referenced: Six-to-eight-week-old male spontaneously hypertensive rats (SHR) or Sprague-Dawley rats are administered various doses of impurity C or olmesartan medoxomil (e.g., 1-10 mg/kg) by oral gavage. Blood samples are collected at various time points post-administration (0.5, 1, 2, 4, 6, 12, 24 hours), and drug concentrations are determined by HPLC-MS/MS to construct concentration-time curves. Blood pressure changes are monitored via tail-cuff method or implanted telemetry system to assess antihypertensive activity. Each experimental group typically contains 6-8 animals.
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| ADME/Pharmacokinetics |
The pharmacokinetics of the parent compound olmesartan medoxomil have been well characterized: Olmesartan medoxomil is rapidly absorbed from the gastrointestinal tract after oral administration and completely hydrolyzed during absorption to the active metabolite olmesartan; the parent drug is not measurable in plasma or excreta. Peak plasma concentrations of olmesartan occur 1-3 hours after administration, with an elimination half-life of 10-15 hours and an absolute bioavailability of approximately 26%-28.6%. Approximately 40% of systemically available olmesartan is excreted renally, with the remainder excreted in feces following biliary secretion. As a derivative retaining both protecting groups, impurity C may undergo hydrolysis similar to olmesartan medoxomil following oral absorption, but its hydrolysis rate and active metabolite generation may be altered due to the structural difference at the C4 position.
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| Toxicity/Toxicokinetics |
Toxicological data for olmesartan medoxomil impurity C are currently limited. As a pharmaceutical impurity, it typically exists only in trace amounts in the drug substance and finished product, so its toxicity contribution at clinical doses is negligible. The quality control standards for olmesartan medoxomil require that known impurities (including impurity C) are controlled within acceptable limits, typically not exceeding 0.1%-0.5%. The parent compound olmesartan medoxomil is generally well-tolerated in clinical use, with the most common adverse reaction being dizziness (approximately 3% incidence). Other adverse reactions include asthenia, angioedema, hyperkalemia, and elevated blood creatinine levels. This compound is intended for drug quality research use only and is not for human therapeutic applications. Standard chemical safety practices should be followed during handling to avoid inhalation, ingestion, or skin contact.
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| References |
|
| Molecular Formula |
C29H28N6O5
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|---|---|
| Molecular Weight |
540.569826126099
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| Exact Mass |
540.212
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| CAS # |
879562-26-2
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| PubChem CID |
44193132
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.975
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
11
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| Heavy Atom Count |
40
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| Complexity |
967
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1OC(COC(C2N(CC3C=CC(C4C(C5NN=NN=5)=CC=CC=4)=CC=3)C(CCC)=NC=2C(C)=C)=O)=C(C)O1
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| InChi Key |
PSFJJUXSEHXDFN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H28N6O5/c1-5-8-24-30-25(17(2)3)26(28(36)38-16-23-18(4)39-29(37)40-23)35(24)15-19-11-13-20(14-12-19)21-9-6-7-10-22(21)27-31-33-34-32-27/h6-7,9-14H,2,5,8,15-16H2,1,3-4H3,(H,31,32,33,34)
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| Chemical Name |
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 5-prop-1-en-2-yl-2-propyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylate
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| Synonyms |
879562-26-2; Dehydro Olmesartan Medoxomil; Olmesartan medoxomil impurity C; (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 1-((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-4-(prop-1-en-2-yl)-2-propyl-1H-imidazole-5-carboxylate; DES(1-hydroxy-1-methylethyl)-(1-methylethenyl)-olmesartan medoxomil;
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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 | 1.8499 mL | 9.2495 mL | 18.4990 mL | |
| 5 mM | 0.3700 mL | 1.8499 mL | 3.6998 mL | |
| 10 mM | 0.1850 mL | 0.9249 mL | 1.8499 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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