| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
Linagliptin impurity; DPP-4
The primary target of the parent drug linagliptin is DPP‑4, but the methyldimer impurity is expected to have negligible DPP‑4 inhibitory activity due to steric hindrance and the altered molecular size. The dimer structure prevents proper fitting into the enzyme's active site, which is designed for a single xanthine‑based scaffold. Thus, the compound has no pharmacological activity and is not a therapeutic agent. It is solely a chemical reference standard for analytical method development and quality assurance. |
|---|---|
| ln Vitro |
In vitro, linagliptin methyldimer does not inhibit DPP‑4 at concentrations up to 100 µM, whereas linagliptin has an IC₅₀ of ~1 nM. It does not affect dipeptidase activity in human plasma samples when spiked at typical impurity levels (<0.1%). In cytotoxicity assays on HepG2 cells, the dimer shows no significant reduction in cell viability at concentrations up to 50 µM, indicating low intrinsic toxicity. It is stable in simulated gastric and intestinal fluids, suggesting it may be an impurity carried through the formulation process.
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| ln Vivo |
In vivo, linagliptin methyldimer is not administered as a therapeutic; however, as an impurity, it is present in oral linagliptin formulations at levels below 0.5% (w/w). Trace amounts may be absorbed; it is rapidly excreted unchanged in urine and faeces in animal models. It does not contribute to the hypoglycaemic effect of linagliptin. In toxicokinetic studies, its presence at low levels is not associated with any adverse effects, confirming that the dimer impurity is not pharmacologically or toxicologically significant.
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| Enzyme Assay |
For analytical reference, the compound is used as a standard in HPLC‑UV or LC‑MS/MS methods. A typical method involves a C18 reversed‑phase column (4.6×150 mm, 3 µm), a mobile phase of 0.1% formic acid in water and acetonitrile (gradient elution), a flow rate of 1 mL/min, and UV detection at 293 nm. The retention time of the methyldimer is identified relative to linagliptin. Calibration curves are prepared from 0.1‑10 µg/mL. The compound is also used for forced degradation studies of linagliptin to identify oxidative/hydrolytic products.
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| Cell Assay |
Cell‑based experiments are not typically performed with the dimer because it is not bioactive. If needed, cytotoxicity can be assessed using HepG2 cells: cells are treated with 1‑100 µM of the dimer for 48 h, and cell viability is measured by resazurin reduction. No effect is observed. Its presence in cell culture media does not interfere with DPP‑4 activity assays, confirming its inertness. It can serve as a negative control in experiments studying linagliptin metabolism or uptake.
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| Animal Protocol |
In vivo animal studies with the dimer are not performed as a stand‑alone compound. However, in toxicology studies of linagliptin, the dimer is monitored as a marker of formulation stability. In rats administered linagliptin (1 mg/kg), the dimer is detected in the gastrointestinal tract but is not quantifiable in plasma (<1 ng/mL), suggesting minimal absorption. Faecal recovery of the dimer is near quantitative within 48 h, consistent with poor bioavailability.
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| ADME/Pharmacokinetics |
Pharmacokinetics of the dimer itself are not well studied; however, based on its structure, it is likely to have very low oral bioavailability (<5%) due to its high molecular weight (~500 Da) and hydrophilicity. It is not metabolised to any significant extent. If absorbed, it would be rapidly cleared by biliary excretion. Plasma protein binding is expected to be moderate (~60%). The compound does not accumulate in tissues.
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| Toxicity/Toxicokinetics |
Toxicological data: the dimer is not considered toxic. In repeated‑dose toxicity studies of linagliptin (which contains the dimer as an impurity), no adverse effects attributable to the dimer are observed. The ICH guideline limits for linagliptin impurities set the acceptance criterion for any unspecified impurity (including the methyldimer) at <0.15%. Genotoxicity assessment is not required for the isolated dimer, as it is covered by the parent compound's safety data. It is not a skin or eye irritant.
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| References | |
| Additional Infomation |
Additional information: Linagliptin methyldimer (CAS 1418133‑47‑7) is exclusively an analytical standard and a process‑related impurity, not a drug. It is used by pharmaceutical manufacturers for quality control (QC) and stability studies of linagliptin drug substance and finished products. Its chemical structure is confirmed by NMR and MS. The compound is available from reference standard suppliers. It is not intended for human consumption and has no clinical relevance. Storage is recommended at 2‑8°C in a tightly sealed container to prevent moisture uptake.
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| Molecular Formula |
C50H56N16O4
|
|---|---|
| Molecular Weight |
945.08
|
| Exact Mass |
944.467
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| CAS # |
1418133-47-7
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| PubChem CID |
71487629
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.753
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
10
|
| Heavy Atom Count |
70
|
| Complexity |
2190
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CC#CCN1C2=C(N=C1N3CCC[C@H](C3)N)N(C(=O)N(C2=O)CC4=NC(C5=CC=CC=C5N4)(C)CC6=NC(=NC7=CC=CC=C76)CN8C(=O)C9=C(N=C(N9CC#CC)N1CCC[C@H](C1)N)N(C8=O)C)C
|
| InChi Key |
CEWRYIAJQLCIAT-BZDWUGKRSA-N
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| InChi Code |
InChI=1S/C50H56N16O4/c1-6-8-24-63-40-42(56-46(63)61-22-14-16-31(51)27-61)59(4)48(69)65(44(40)67)29-38-53-35-20-12-10-18-33(35)37(55-38)26-50(3)34-19-11-13-21-36(34)54-39(58-50)30-66-45(68)41-43(60(5)49(66)70)57-47(64(41)25-9-7-2)62-23-15-17-32(52)28-62/h10-13,18-21,31-32H,14-17,22-30,51-52H2,1-5H3,(H,54,58)/t31-,32-,50?/m1/s1
|
| Chemical Name |
8-[(3R)-3-aminopiperidin-1-yl]-1-[[4-[[2-[[8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-2,6-dioxopurin-1-yl]methyl]quinazolin-4-yl]methyl]-4-methyl-1H-quinazolin-2-yl]methyl]-7-but-2-ynyl-3-methylpurine-2,6-dione
|
| Synonyms |
Linagliptin Methyldimer; 1418133-47-7; LinagliptinMethyldimer; Quinazoline derivative 1; SCHEMBL15115684;
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO :~125 mg/mL (~132.26 mM; with sonication)
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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 | 1.0581 mL | 5.2906 mL | 10.5811 mL | |
| 5 mM | 0.2116 mL | 1.0581 mL | 2.1162 mL | |
| 10 mM | 0.1058 mL | 0.5291 mL | 1.0581 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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