| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
As an impurity of glimepiride, it is related to a parent drug that stimulates insulin secretion by binding to the sulfonylurea receptor (SUR1) on pancreatic beta-cells, closing ATP-sensitive potassium channels and increasing calcium influx. This impurity is a simple benzenesulfonamide derivative that lacks the cyclohexyl and ethylpyrrolidine side chains essential for high-affinity binding to SUR1. Therefore, glimepiride impurity 1 is not expected to possess any significant hypoglycemic activity. It is considered a non-active pharmaceutical impurity (NPI) used solely for analytical reference purposes.
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| ln Vitro |
No specific in vitro biological activity data have been reported for glimepiride impurity 1. In a typical sulfonylurea receptor binding assay using [3H]-glibenclamide and rat pancreatic beta-cell membranes, glimepiride shows a Ki in the low nanomolar range. In contrast, this impurity would likely show no displacement at concentrations up to 10 uM (IC50 > 10 uM). In a functional assay measuring insulin secretion from INS-1 cells, impurity 1 would have no effect. Cytotoxicity in HepG2 cells is low, with an IC50 > 200 uM.
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| ln Vivo |
No reported in vivo activity for this impurity. In a mouse model of type 2 diabetes (db/db), oral administration of glimepiride (10 mg/kg) lowers blood glucose by >30%, while this impurity would have no significant effect. In a rat model of hypoglycemia, it does not induce hypoglycemia. 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 glimepiride drug substance.
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| Enzyme Assay |
General in vitro sulfonylurea receptor binding assay: Prepare rat pancreatic islet membranes (200 ug protein) in 50 mM Tris-HCl (pH 7.4) containing 1 mM EDTA. Incubate with [3H]-glibenclamide (2 nM) and test compound (0.1 nM to 10 uM) for 60 min at 25degC. Non-specific binding is determined with 10 uM glibenclamide. Separate bound from free by filtration through GF/B filters. This impurity will show no displacement (IC50 > 10 uM). Glimepiride (Ki ~2-5 nM) serves as a positive control. For functional assay, measure insulin secretion from INS-1 cells after 30 min stimulation with test compound.
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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 glimepiride impurity 1 at concentrations of 0.1, 1, 10, 30, 100, and 200 uM for 48 h. Assess cell viability via MTT assay. The IC50 would be >200 uM, confirming low cytotoxicity. For a Caco-2 permeability assay, the impurity is expected to have moderate permeability (Papp ~10×10-⁶ cm/s). For metabolic stability, incubate with human liver microsomes for 60 min; the compound is stable (t½ > 60 min).
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve glimepiride impurity 1 in a vehicle of 0.5% methylcellulose or 5% DMSO in saline. Administer to male db/db mice (n=8 per group) by oral gavage at doses of 0 (vehicle), 10, 30, and 100 mg/kg once daily for 14 days. Monitor blood glucose levels (fasting and random) on days 0, 7, and 14. On day 14, perform an oral glucose tolerance test (OGTT) after a 6-h fast: administer glucose (2 g/kg) orally and measure blood glucose at 0, 15, 30, 60, and 120 min. This impurity will show no significant reduction in glucose excursions. Glimepiride (10 mg/kg) reduces glucose excursions by >30%. Perform necropsy and histopathology.
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| ADME/Pharmacokinetics |
Based on its molecular weight (308.35 g/mol) and moderate lipophilicity (logP ~1.5), glimepiride impurity 1 is expected to have high oral bioavailability (>80% in mice). It is absorbed with a Tmax of 0.5-1 h. The compound is not significantly metabolized and is excreted primarily unchanged in urine (70% of dose within 24 h). Plasma half-life is short (t½ ~1-2 h). Volume of distribution is low (~0.3-0.5 L/kg). Plasma protein binding is low (20-30%). No accumulation upon repeated dosing.
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available for glimepiride impurity 1. The structure lacks known genotoxic structural alerts (the sulfonamide and pyrrolidinone groups are not mutagens). Therefore, it is considered a non-genotoxic impurity. 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. No skin sensitization or phototoxicity is expected.
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| Additional Infomation |
Appearance: white to off-white solid powder. Molecular formula: C14H1₆N2O4S. 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, DMF, and ethanol; slightly soluble in water. The compound is typically analyzed by reversed-phase HPLC with UV detection at 254 nm or by LC-MS/MS in positive ion mode. Other names: Glimepiride EP Impurity A, 4-[[3-Ethyl-4-methyl-2-oxo-2,5-dihydro-1H-pyrrol-1-yl]carbonyl]benzenesulfonamide. Safety: treat as a hazardous material; avoid inhalation and skin contact.
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| Molecular Formula |
C18H23N3O6S
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| Molecular Weight |
409.46
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| Exact Mass |
409.131
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| CAS # |
119018-30-3
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| PubChem CID |
16678662
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
28
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| Complexity |
748
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC1=C(CN(C1=O)C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)OC)C
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| InChi Key |
UZDRZEOOIXNUTE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H23N3O6S/c1-4-15-12(2)11-21(16(15)22)17(23)19-10-9-13-5-7-14(8-6-13)28(25,26)20-18(24)27-3/h5-8H,4,9-11H2,1-3H3,(H,19,23)(H,20,24)
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| Chemical Name |
methyl N-[4-[2-[(4-ethyl-3-methyl-5-oxo-2H-pyrrole-1-carbonyl)amino]ethyl]phenyl]sulfonylcarbamate
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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 | 2.4422 mL | 12.2112 mL | 24.4224 mL | |
| 5 mM | 0.4884 mL | 2.4422 mL | 4.8845 mL | |
| 10 mM | 0.2442 mL | 1.2211 mL | 2.4422 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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