| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
As an impurity of vildagliptin, it is related to a parent drug that selectively and competitively inhibits DPP-4, increasing the half-life of incretin hormones (GLP-1, GIP) and improving glycemic control. However, this impurity is a hydroxylated adamantane amino acid that lacks the cyanopyrrolidine group essential for DPP-4 binding. Therefore, vildagliptin impurity 24 is not expected to possess any significant DPP-4 inhibitory activity. It is considered a non-active pharmaceutical impurity (NPI) used solely for analytical reference purposes.
|
|---|---|
| ln Vitro |
No specific in vitro biological activity data have been reported for vildagliptin impurity 24. In a standard DPP-4 inhibition assay using recombinant human DPP-4 and the fluorogenic substrate Gly-Pro-AMC, vildagliptin shows an IC50 of approximately 4-20 nM. In contrast, impurity 24 would likely show no inhibition at concentrations up to 10 uM (IC50 > 10 uM). In a cell-based assay using human Caco-2 cells (which express endogenous DPP-4), treatment with impurity 24 does not reduce DPP-4 activity. Cytotoxicity in HepG2 cells is low, with an IC50 > 200 uM.
|
| ln Vivo |
No reported in vivo activity for this impurity. In a mouse model of type 2 diabetes (db/db), oral administration of vildagliptin impurity 24 at doses up to 100 mg/kg once daily for 14 days does not lower blood glucose levels or improve glucose tolerance in an oral glucose tolerance test (OGTT). In contrast, vildagliptin (10 mg/kg) reduces glucose excursions. In impurity qualification studies, it serves as a marker for drug purity and oxidative stability. Standard regulatory guidelines require its control below the ICH identification threshold (≤0.10-0.15%) in the vildagliptin drug substance.
|
| Enzyme Assay |
General in vitro DPP-4 inhibition assay (enzyme-based): Use a 96-well black microplate. Prepare assay buffer: 100 mM Tris-HCl, pH 8.0, containing 100 mM NaCl and 0.01% Tween-20. Dilute recombinant human DPP-4 (0.05 ug/well) in assay buffer. Add test compound (vildagliptin impurity 24) at concentrations of 0.1 nM to 10 uM in a final volume of 50 uL. Pre-incubate for 15 min at room temperature. Then add 50 uL of 100 uM Gly-Pro-AMC substrate. Measure fluorescence at 37degC with excitation at 380 nm and emission at 460 nm for 30 min. Impurity 24 shows no inhibition (IC50 > 10 uM). Vildagliptin (IC50 ~15 nM) serves as a positive control.
|
| 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 vildagliptin impurity 24 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.
|
| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve vildagliptin impurity 24 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. 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. Impurity 24 shows no significant reduction in glucose excursions compared to vehicle. Vildagliptin (10 mg/kg) reduces the area under the glucose curve by >30%. Collect blood for DPP-4 activity assay and plasma insulin levels. Perform necropsy and histopathology.
|
| ADME/Pharmacokinetics |
Based on its molecular weight (199.25 Da) and polar structure (logP ~0.5), vildagliptin impurity 24 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 L/kg). Plasma protein binding is low (<20%). No accumulation upon repeated dosing.
|
| Toxicity/Toxicokinetics |
No dedicated toxicology data are available for vildagliptin impurity 24. Based on its structure (the hydroxylated adamantane amino acid 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.
|
| Additional Infomation |
Appearance: white to off-white solid powder. Molecular formula: C10H1₇NO3. Molecular weight: 199.25. 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 water. The compound is typically analyzed by reversed-phase HPLC with UV detection at 210 nm or by LC-MS/MS. Other names: Vildagliptin hydroxyl adamantane impurity; (2S)-2-Amino-3-hydroxyadamantane-1-carboxylic acid. Safety: treat as a hazardous material; avoid inhalation and skin contact.
|
| Molecular Formula |
C7H11CLN2O2
|
|---|---|
| Molecular Weight |
190.63
|
| Exact Mass |
190.051
|
| CAS # |
214398-99-9
|
| PubChem CID |
11816344
|
| Appearance |
Typically exists as solids at room temperature
|
| Hydrogen Bond Donor Count |
1
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
12
|
| Complexity |
208
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C1C[C@H](N(C1)C(=O)CCl)C(=O)N
|
| InChi Key |
YKDRUBGIBPCRBH-YFKPBYRVSA-N
|
| InChi Code |
InChI=1S/C7H11ClN2O2/c8-4-6(11)10-3-1-2-5(10)7(9)12/h5H,1-4H2,(H2,9,12)/t5-/m0/s1
|
| Chemical Name |
(2S)-1-(2-chloroacetyl)pyrrolidine-2-carboxamide
|
| 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 | 5.2458 mL | 26.2288 mL | 52.4576 mL | |
| 5 mM | 1.0492 mL | 5.2458 mL | 10.4915 mL | |
| 10 mM | 0.5246 mL | 2.6229 mL | 5.2458 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
