| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Tadalafil-d3 targets the same enzyme as tadalafil, which is phosphodiesterase 5 (PDE5). Tadalafil is a potent and selective inhibitor of PDE5 with an IC50 of 1.2 nM. As a stable isotope-labeled compound, Tadalafil-d3 is not used for pharmacological activity studies but serves as a tracer to accurately measure the pharmacokinetics and metabolism of tadalafil in research and clinical settings.
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|---|---|
| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
As a stable isotope-labeled internal standard, Tadalafil-d3 is not tested for standalone in vitro activity. The parent drug tadalafil has potent in vitro activity: it inhibits PDE5 isolated from human platelets with an IC50 of 1.2 nM and is highly selective over PDE1-4 and 7-10 (IC50s 9.2-280 microM). Tadalafil also inhibits PDE11 (IC50 11 nM). In cell-based assays, tadalafil increases cGMP levels in smooth muscle cells. |
| ln Vivo |
Tadalafil-d3 itself has no intrinsic in vivo activity. The parent drug tadalafil is an FDA-approved drug for erectile dysfunction, pulmonary arterial hypertension, and benign prostatic hyperplasia. In vivo, tadalafil (10 mg/kg) decreases production of proinflammatory cytokines TNF-alpha, IL-1beta, and IL-6 and improves renal function in a rat model of ischemia/reperfusion injury. It also reduces development of tobacco smoke-induced emphysema and pulmonary hypertension in mice.
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| Enzyme Assay |
Tadalafil-d3 is used as an internal standard in cell-free LC-MS/MS assays. A stock solution is prepared by dissolving the compound in methanol or acetonitrile (e.g., 1 mg/mL). A fixed amount (e.g., 10-500 ng/mL) is spiked into plasma, urine, or other biological matrices before sample preparation. After protein precipitation with acetonitrile and centrifugation, the supernatant is analyzed by LC-MS/MS. The analyte-to-internal standard peak area ratio is used for quantification.
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| Cell Assay |
Tadalafil-d3 is not used as a treatment in cell-based studies. It is added post-treatment to cell lysates or culture media as an internal standard. For example, cells (e.g., smooth muscle cells or endothelial cells) are treated with tadalafil. After incubation, the culture medium is collected, and Tadalafil-d3 is added at a fixed concentration. Following protein precipitation and centrifugation, the sample is analyzed by LC-MS/MS to quantify tadalafil uptake and metabolism.
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| Animal Protocol |
For in vivo pharmacokinetic studies, Tadalafil-d3 is not administered to animals independently. It is used as an internal standard for quantifying tadalafil in samples from animals dosed with the unlabeled drug. For example, rats or dogs are administered tadalafil (e.g., 1-10 mg/kg orally). Blood samples are collected at multiple time points. Tadalafil-d3 is added to plasma samples at a known concentration, and samples are processed and analyzed by LC-MS/MS to determine tadalafil concentration-time profiles.
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| ADME/Pharmacokinetics |
Tadalafil-d3 has no independent pharmacokinetic parameters. The unlabeled tadalafil has an absolute oral bioavailability of approximately 46%, is highly bound to human plasma proteins (∼85%), and has a terminal elimination half-life of approximately 29 hours in humans. The volume of distribution is about 63 L, and clearance is about 2.5 L/h. The deuterated standard follows identical ADME properties.
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| Toxicity/Toxicokinetics |
Tadalafil-d3 is a stable isotope-labeled standard and is considered non-toxic at the trace levels used in analytical research (microgram to milligram quantities). The unlabeled tadalafil is generally well-tolerated at therapeutic doses, with side effects including headache, indigestion, back pain, muscle aches, flushing, and stuffy nose. The deuterated version is chemically identical and has the same safety profile. Standard laboratory precautions apply.
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| References |
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| Additional Infomation |
Tadalafil-d3 is not a drug but a deuterium-labeled stable isotope internal standard. It has no approved therapeutic status and is not intended for human consumption. It is used for analytical method development, method validation (AMV), quality control (QC) during commercial production of tadalafil, and for pharmacokinetic studies. Tadalafil is an FDA-approved drug (Cialis®) for erectile dysfunction, pulmonary arterial hypertension, and benign prostatic hyperplasia.
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| Molecular Formula |
C22H16D3N3O4
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|---|---|
| Molecular Weight |
392.42
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| Exact Mass |
389.138
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| CAS # |
960226-55-5
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| Related CAS # |
Nortadalafil;171596-36-4;Tadalafil;171596-29-5
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| PubChem CID |
46782966
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| Appearance |
White to off-white solid powder
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| LogP |
2.087
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
29
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| Complexity |
702
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| Defined Atom Stereocenter Count |
2
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| SMILES |
[2H]C([2H])([2H])N1CC(=O)N2[C@@H](C1=O)CC3=C([C@H]2C4=CC5=C(C=C4)OCO5)NC6=CC=CC=C36
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| InChi Key |
WOXKDUGGOYFFRN-WFMNTJQSSA-N
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| InChi Code |
InChI=1S/C22H19N3O4/c1-24-10-19(26)25-16(22(24)27)9-14-13-4-2-3-5-15(13)23-20(14)21(25)12-6-7-17-18(8-12)29-11-28-17/h2-8,16,21,23H,9-11H2,1H3/t16-,21-/m1/s1/i1D3
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| Chemical Name |
(2R,8R)-2-(1,3-benzodioxol-5-yl)-6-(trideuteriomethyl)-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione
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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) |
DMSO: ~50 mg/mL (~127.4 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5483 mL | 12.7415 mL | 25.4829 mL | |
| 5 mM | 0.5097 mL | 2.5483 mL | 5.0966 mL | |
| 10 mM | 0.2548 mL | 1.2741 mL | 2.5483 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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