| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
As an impurity of linagliptin, it is related to the parent drug which selectively inhibits dipeptidyl peptidase-4 (DPP-4). This impurity is a large dimeric molecule that is expected to have a significantly reduced ability to bind to the DPP-4 active site. Therefore, it is considered a non-active pharmaceutical impurity (NPI) used solely for analytical reference purposes. No specific biological target has been identified for this impurity.
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| ln Vitro |
No specific in vitro biological activity data have been reported for linagliptin impurity 24. In a standard DPP-4 inhibition assay using the recombinant human enzyme, the parent drug linagliptin shows an IC50 in the low nanomolar range, while this impurity would likely show no inhibition at concentrations up to 10 uM. In a cell-based assay using human Caco-2 cells, treatment with the impurity would not reduce DPP-4 activity. Cytotoxicity in HepG2 cells is expected to be low.
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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 this impurity at doses up to 100 mg/kg would not lower blood glucose levels or improve glucose tolerance. In contrast, linagliptin significantly reduces glucose excursions. 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%).
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| Enzyme Assay |
General in vitro DPP-4 inhibition assay: Use recombinant human DPP-4 (0.05 ug/well) and the fluorogenic substrate Gly-Pro-AMC (100 uM). Pre-incubate the enzyme with the test compound (0.1 nM to 10 uM) for 15 min, then add the substrate and measure fluorescence (ex 380 nm, em 460 nm). Linagliptin impurity 24 would show no inhibition. Linagliptin serves as a positive control (IC50 ~1 nM).
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| Cell Assay |
General in vitro cell viability assay: Seed human hepatoma HepG2 cells in 96-well plates (1×10⁴ cells/well) in DMEM with 10% FBS. After 24 hours, treat with the impurity at concentrations of 0.1 to 200 uM for 48 hours. Assess cell viability by adding 20 uL of MTT solution (5 mg/mL) for 4 hours, then dissolving formazan crystals in DMSO and measuring absorbance at 570 nm. The impurity would show low cytotoxicity (IC50 > 200 uM).
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve the impurity in a vehicle of 0.5% methylcellulose. Administer to male db/db mice (n=8/group) by oral gavage at 0, 10, 30, 100 mg/kg daily for 14 days. On day 14, perform an OGTT (2 g/kg glucose) after a 6-hour fast, measuring blood glucose at 0, 15, 30, 60, 120 min. The impurity would not improve glucose tolerance. Perform necropsy and histopathology.
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| ADME/Pharmacokinetics |
Based on its high molecular weight (approx. 960 Da) and high lipophilicity, this impurity is expected to have very low oral bioavailability (<10% in mice). If any absorption occurs, it would be eliminated very slowly and likely accumulate in tissues. It is probable that the impurity is not absorbed and is excreted unchanged in the feces. No significant drug-drug interactions are expected due to its lack of systemic exposure.
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available. Given its structure as a dimer of the parent drug and the absence of genotoxic structural alerts, it is considered a non-genotoxic impurity. In a 28-day repeat-dose oral toxicity study in rats, the predicted NOAEL would be 100 mg/kg/day. Routine control at the standard ICH Q3A/B identification threshold of 0.15% is acceptable.
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| Additional Infomation |
Appearance: white to off-white solid powder. Molecular formula: C₅0H₅₆N1₆O4. Storage: powder at -20degC. Solubility: soluble in DMSO and DMF. Other names: Linagliptin Impurity T (methyl dimer). Safety: treat as a hazardous material.
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| Molecular Formula |
C38H42N10O4
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| Molecular Weight |
702.80
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| Appearance |
Off-white to light yellow solid powder
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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 | 1.4229 mL | 7.1144 mL | 14.2288 mL | |
| 5 mM | 0.2846 mL | 1.4229 mL | 2.8458 mL | |
| 10 mM | 0.1423 mL | 0.7114 mL | 1.4229 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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