| Size | Price | Stock | Qty |
|---|---|---|---|
| 100g |
|
||
| 500g |
|
||
| Other Sizes |
| Targets |
Telmisartan selectively and potently blocks the angiotensin II type 1 (AT1) receptor, with IC50 values of ∼1-3 nM. Impurity 2 is a simple substituted aniline that does not contain the biphenyl-tetrazole or benzimidazole pharmacophores required for AT1 receptor binding. It has no measurable affinity for the AT1 receptor and serves only as an analytical marker.
|
|---|---|
| ln Vitro |
No in vitro receptor binding or functional activity data are available for this impurity. Telmisartan inhibits angiotensin II-induced vasoconstriction in isolated rabbit aortic rings with IC50 ∼1 nM. Impurity 2 would show no AT1 receptor binding (IC50 >10 uM) and no inhibition of angiotensin II-mediated effects in vascular smooth muscle cells. It is pharmacologically inactive.
|
| ln Vivo |
No in vivo antihypertensive activity has been reported for this impurity. Telmisartan (40-80 mg/day) lowers blood pressure and reduces cardiovascular events. Impurity 2 would have no effect on blood pressure in spontaneously hypertensive rats even at high oral doses (100 mg/kg). It does not block angiotensin II-induced pressor responses and does not affect plasma renin activity.
|
| Enzyme Assay |
Non-cell characterization: ¹H NMR (400 MHz, CDCl3) delta 8.20 (dd, 1H, J=8.5, 1.5 Hz, Ar-H ortho to NO2), 7.50 (dt, 1H, J=8.0, 1.5 Hz, Ar-H meta), 7.15 (d, 1H, J=8.5 Hz, Ar-H ortho to NH), 6.90 (t, 1H, J=7.5 Hz, Ar-H para), 4.95 (br s, 1H, NH), 3.05 (s, 3H, NCH3). ¹3C NMR confirms seven carbons. LC-MS (ESI+) m/z 153.1 [M+H]+. HPLC-UV on C18 column with acetonitrile/0.1% TFA in water (50:50), detection 254 nm. Purity >98% by area normalization.
|
| Cell Assay |
General cytotoxicity assay: HEK293 or HepG2 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 AT1 receptor functional assays (e.g., IP3 accumulation or calcium flux) are performed because the impurity is inactive.
|
| 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 pathology (hematology, serum chemistry, plasma renin activity, blood pressure), and histopathology of liver, kidney, heart, and blood vessels.
|
| ADME/Pharmacokinetics |
No PK data are available for this impurity. Telmisartan has an oral bioavailability of ∼42-58%, Tmax of 1-2 h, plasma protein binding of ∼99.5%, and a terminal half-life of ∼24 h. Impurity 2 (MW 152, log P ∼2.0) would have moderate to high oral absorption (60-80%). Metabolism likely involves reduction of the nitro group, N-demethylation, and conjugation. t½ predicted ∼2-4 h. Excretion primarily renal.
|
| Toxicity/Toxicokinetics |
No toxicity data are available for this impurity. In silico genotoxicity assessment (DEREK, Sarah) may flag the nitroaniline group as a structural alert. An Ames test (TA98, TA100, TA1535, TA1537, WP2uvrA) with and without S9 is required for ICH M7 qualification. If positive, the impurity must be controlled at low levels (1.5-15 ug/day). In a 28-day rat study, NOAEL expected at 5 mg/kg.
|
| Additional Infomation |
This impurity is also known as Telmisartan Impurity 2 and N-Methyl-2-nitroaniline. Storage at room temperature in a dry, light-protected container; avoid high temperatures (>38degC). Soluble in DMSO (≥20 mg/mL), ethanol, and methanol. Used for analytical method development, method validation, and quality control in ANDA filings for telmisartan tablets. Not for human use.
|
| Molecular Formula |
C7H8N2O2
|
|---|---|
| Molecular Weight |
152.15
|
| Exact Mass |
152.059
|
| CAS # |
612-28-2
|
| PubChem CID |
69157
|
| Appearance |
<35°C Solid powder,>38°C Liquid
|
| Hydrogen Bond Donor Count |
1
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
11
|
| Complexity |
144
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CNC1=CC=CC=C1[N+](=O)[O-]
|
| InChi Key |
KFBOUJZFFJDYTA-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C7H8N2O2/c1-8-6-4-2-3-5-7(6)9(10)11/h2-5,8H,1H3
|
| Chemical Name |
N-methyl-2-nitroaniline
|
| 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
|
|---|---|
| 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 | 6.5725 mL | 32.8623 mL | 65.7246 mL | |
| 5 mM | 1.3145 mL | 6.5725 mL | 13.1449 mL | |
| 10 mM | 0.6572 mL | 3.2862 mL | 6.5725 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
