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| 1mg |
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| Targets |
Dabigatran etexilate is a double prodrug that is hydrolyzed in vivo to produce the active moiety dabigatran, which is a direct thrombin inhibitor (Ki = 4.5 nM for thrombin). As an internal standard, dabigatran etexilate-d13 does not itself exert any pharmacological effect at the concentrations used in analytical workflows, but it tracks the metabolic conversion of the parent prodrug to dabigatran in biological samples.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
Dabigatran etexilate-d13 is not employed in in vitro functional cellular assays because it is an analytical standard. However, the unlabeled dabigatran (the active metabolite) shows concentration-dependent inhibition of soluble thrombin activity and thrombin-induced platelet aggregation (IC50 = 10 nM) in platelet-rich plasma assays. It demonstrates no significant inhibitory activity against a wide panel of other serine proteases at therapeutic concentrations, confirming its selectivity for thrombin. |
| ln Vivo |
As a deuterium-labeled internal standard, dabigatran etexilate-d13 is not used as a pharmacological agent in animal models. Nevertheless, the unlabeled parent compound, dabigatran etexilate, is orally active and shows efficacy in standard animal thrombosis models (e.g., rat arteriovenous shunt model) at doses of 1-10 mg/kg. Oral administration produces dose-dependent prolongation of clotting times (aPTT, ECT, TT) and reduces thrombus weight. Deuteration does not impact the fundamental anticoagulant properties of the molecule but aids in accurate quantification of these effects.
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| Enzyme Assay |
Dabigatran etexilate-d13 is an internal standard and does not undergo conventional in vitro receptor binding assays. Instead, its identity and purity are confirmed by NMR and HPLC-MS prior to use. For LC-MS/MS method development, a standard solution of dabigatran etexilate-d13 in acetonitrile or methanol is typically prepared. The compound is characterized by its molecular formula C34H28D13N7O5, and its deuterium enrichment ensures a mass shift relative to the unlabeled analyte for specific MRM transitions.
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| Cell Assay |
Dabigatran etexilate-d13 is not used for cell-based assays. As an LC-MS/MS internal standard, the procedure is as follows: a working solution of the d13-labeled internal standard is spiked into plasma, serum, urine, or tissue homogenates prior to sample preparation. The samples undergo protein precipitation (e.g., with acetonitrile containing 0.1% formic acid), centrifugation, and supernatant injection onto an LC-MS/MS system. The area ratio of the unlabeled dabigatran etexilate to the d13 standard is used to back-calculate concentrations from a calibration curve.
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| Animal Protocol |
Dabigatran etexilate-d13 is primarily used as a calibrant and internal standard in LC-MS/MS bioanalytical methods for pharmacokinetic studies of dabigatran etexilate in animal models. A typical study design involves collecting blood samples at predetermined time points (e.g., 0, 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose) from dosed animals. The d13-labeled internal standard is added to each plasma sample (e.g., 100 microL) at a fixed concentration before extraction to normalize the analytical signal. PK parameters (AUC, Cmax, Tmax, half-life) are calculated using non-compartmental analysis.
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| ADME/Pharmacokinetics |
Dabigatran etexilate-d13 is an internal standard; its PK profile mirrors that of dabigatran etexilate. The unlabeled dabigatran etexilate is rapidly absorbed and converted to dabigatran via esterase-mediated hydrolysis. Peak concentrations of the active moiety are reached approximately 1.5-3 hours post-dose. The terminal elimination half-life of dabigatran is 12-14 hours in healthy subjects, with renal excretion being the primary clearance pathway (approx. 80%). The d13-labeled standard accounts for matrix effects and ionization variability in bioanalysis.
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| Toxicity/Toxicokinetics |
As a deuterium-labeled reagent, dabigatran etexilate-d13 poses negligible toxicity risk when handled properly in the laboratory with standard personal protective equipment (PPE). The unlabeled parent drug dabigatran etexilate exhibits dose-limiting toxicities in the form of hemorrhagic events (bleeding) at supratherapeutic doses. No significant genotoxicity or carcinogenicity has been reported for dabigatran. Nausea, dyspepsia, and diarrhea are common non-hemorrhagic adverse effects in clinical use.
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| References |
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Wienen W, et al. In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally activeprodrug, dabigatran etexilate. Thromb Haemost. 2007 Jul;98(1):155-62. [3]. Blair HA, Keating GM. Dabigatran Etexilate: A Review in Nonvalvular Atrial Fibrillation. Drugs. 2017;77(3):331-344. |
| Additional Infomation |
Dabigatran etexilate (BIBR 1048) is the double prodrug form of the active anticoagulant dabigatran. It is the first orally available direct thrombin inhibitor. Dabigatran etexilate is a substrate of P-glycoprotein (ABCB1) but is not metabolized by CYP450 isozymes, resulting in a low potential for CYP-mediated drug-drug interactions. The oral prodrug approach was necessary to improve the very low oral bioavailability of the active dabigatran. Dabigatran etexilate is clinically approved for the prevention of stroke and systemic embolism in atrial fibrillation, treatment of venous thromboembolism, and thromboprophylaxis in orthopedic surgery. Dabigatran etexilate-d13 is strictly for research purposes only and not intended for human therapeutic use.
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| Molecular Formula |
C34H28D13N7O5
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| Molecular Weight |
640.81
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| Related CAS # |
Dabigatran etexilate;211915-06-9
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| Appearance |
Typically exists as solid at room temperature
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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 | 1.5605 mL | 7.8026 mL | 15.6052 mL | |
| 5 mM | 0.3121 mL | 1.5605 mL | 3.1210 mL | |
| 10 mM | 0.1561 mL | 0.7803 mL | 1.5605 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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