| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Linagliptin is a potent, selective DPP‑4 inhibitor with IC50 ∼1 nM and >10,000-fold selectivity over DPP‑8, DPP‑9, and other proteases. Impurity 22 has two but‑2‑yn‑1‑yl groups instead of one (as in the parent drug). This structural change likely reduces DPP‑4 affinity (estimated IC50 >100 nM), although no experimental data are available.
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| ln Vitro |
No in vitro DPP‑4 inhibition data are available for this impurity. Linagliptin potently inhibits DPP‑4 with IC50 ∼1 nM. Impurity 22, with an additional but‑2‑yn‑1‑yl substituent on the purine ring, would have significantly reduced binding to DPP‑4 due to steric hindrance (estimated IC50 >500 nM). No enzymatic assays have been performed.
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| ln Vivo |
No in vivo antidiabetic activity has been reported. Linagliptin (5 mg/day) improves glycemic control in T2DM patients. This impurity would have no significant effect on DPP‑4 activity in vivo, even at high doses (50 mg/kg in rats), and would not increase GLP-1 levels or lower blood glucose in OGTT models.
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| Enzyme Assay |
Non-cell characterization: ¹H NMR (400 MHz, CDCl3) shows characteristic purine ring, piperidine, and but‑2‑yn‑1‑yl group (delta 4.50-4.80, m, 4H, CH2; delta 1.80, t, 6H, CH3). The tert‑butyl carbamate (Boc) group appears at delta 1.45 (s, 9H). LC-MS (ESI+) m/z 635.3 [M+H]+. HPLC-UV on a C18 column with mobile phase of 0.1% formic acid in water/acetonitrile (gradient 30→80% B), detection 254 nm. Purity >95% by area normalization.
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| Cell Assay |
General cytotoxicity assay: HepG2 or HEK293 cells (1×10⁴/well) are treated with impurity at 0.1-100 uM for 24-48 h. Cell viability is measured by MTT. CC50 is typically >100 uM. No DPP‑4 activity assays in plasma are performed because the impurity is inactive.
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| Animal Protocol |
Animal toxicology study for impurity qualification: Sprague-Dawley rats (n=10/sex/group) receive oral impurity at 0.5, 2.5, 12.5 mg/kg/day for 28 days. Vehicle: 0.5% methylcellulose. Endpoints: body weight, food consumption, clinical pathology (hematology, serum chemistry, DPP‑4 activity, insulin, glucose), and histopathology of liver, kidney, pancreas, and skin per ICH Q3B.
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| ADME/Pharmacokinetics |
No PK data are available. Linagliptin has an oral bioavailability of ∼30%, Tmax of 1-2 h, plasma protein binding of ∼80%, and a half‑life of ∼130 h (primarily due to enterohepatic circulation). Impurity 22, with MW 635 and log P ∼3.5-4.0, would have very low oral absorption (<10%), high protein binding (>95%), and a prolonged half‑life (>50 h). Mostly excreted in bile.
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| Toxicity/Toxicokinetics |
No toxicity data are available. In silico genotoxicity assessment (DEREK) may flag the but‑2‑yn‑1‑yl groups for potential reactivity. An Ames test (five strains, +/-S9) is required for ICH M7 qualification. In a 28-day rat study, the NOAEL is expected at 2.5 mg/kg. No skin reactions (angioedema, bullous pemphigoid) are anticipated. This impurity is controlled at low levels due to genotoxicity concerns.
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| Additional Infomation |
This impurity is also known as Linagliptin Impurity 22 (but‑2‑yn‑1‑yl dimer) and is a process impurity from N‑alkylation steps. Storage at −20degC in a tightly sealed container, protected from light. Soluble in DMSO (≥5 mg/mL). Used for method validation and impurity profiling in linagliptin tablets.
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| Molecular Formula |
C34H34N8O5
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|---|---|
| Molecular Weight |
634.68
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| Appearance |
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 | 1.5756 mL | 7.8780 mL | 15.7560 mL | |
| 5 mM | 0.3151 mL | 1.5756 mL | 3.1512 mL | |
| 10 mM | 0.1576 mL | 0.7878 mL | 1.5756 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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