| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
As a stable isotope-labeled internal standard, (rac)-Rivastigmine-d6 does not have a primary pharmacological target in bioanalytical contexts. The unlabeled parent compound, rivastigmine, is a pseudo-irreversible inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), used clinically for the treatment of Alzheimer‘s and Parkinson‘s disease dementia.
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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].
The unlabeled rivastigmine inhibits both butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) with IC50 values of 0.037 uM (37 nM) for BChE and 4.15 uM for AChE. It increases levels of secreted amyloid precursor protein (sAPP) and decreases levels of soluble amyloid-beta (1-40) in degenerating primary rat neurons at concentrations of 5 and 10 uM. The deuterated standard is not used for measuring intrinsic biological activity. |
| ln Vivo |
In vivo, unlabeled rivastigmine is used clinically for the treatment of dementia associated with Alzheimer‘s disease and Parkinson‘s disease. In a rat model of Alzheimer‘s disease, rivastigmine (1 mg/kg/day) inhibits the formation of amyloid plaques in brain sections, reverses cognitive deficits in the Morris water maze, and shows antidepressant and anxiolytic effects in the chronic mild stress model.
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| Enzyme Assay |
(rac)-Rivastigmine-d6 is not used in non-cellular enzyme assays as a test compound. Instead, it is used as an internal standard in such assays for quantification purposes. A known, fixed amount of the deuterated internal standard is spiked into a biological sample containing unlabeled rivastigmine. The sample is processed by protein precipitation and then analyzed by LC-MS/MS.
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| Cell Assay |
No cell-based experiments are performed with the deuterated standard. For studying the pharmacology of the unlabeled parent, primary embryonic rat neurons undergoing degeneration are treated with rivastigmine at concentrations of 5 and 10 uM. The levels of secreted amyloid precursor protein (sAPP) and amyloid-beta (Abeta) peptides in the culture medium are then quantified by ELISA to assess the effect on amyloid processing.
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| Animal Protocol |
A standard in vivo protocol for measuring the pharmacokinetics of rivastigmine involves administering unlabeled rivastigmine to rats or human subjects. Blood or plasma samples are collected at multiple time points post-dose. A constant, known amount of (rac)-Rivastigmine-d6 is spiked into each sample as an internal standard. Following protein precipitation or solid-phase extraction, samples are analyzed by LC-MS/MS to quantify the unlabeled rivastigmine concentration.
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| ADME/Pharmacokinetics |
(rac)-Rivastigmine-d6 is chemically identical to the unlabeled analyte (rivastigmine) except for a +6 Da mass shift due to six deuterium atoms, resulting in virtually identical extraction recovery, chromatographic retention time, and ionization efficiency. It is stable under typical LC-MS conditions and is a deuterium-labeled standard designed for use in GC- or LC-MS quantification.
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| Toxicity/Toxicokinetics |
No direct toxicological data is provided for the deuterated standard, as it is used at trace analytical levels. The unlabeled rivastigmine has a well-characterized clinical safety profile; its most common side effects are cholinergic in nature, primarily gastrointestinal (nausea, vomiting, diarrhea, anorexia), and are related to its mechanism of acetylcholinesterase inhibition in the peripheral nervous system.
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| References |
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| Additional Infomation |
(rac)-Rivastigmine-d6 is a critical quality control tool for the pharmaceutical analysis of rivastigmine. The use of a stable isotope-labeled internal standard is the gold standard for meeting regulatory guidelines for bioanalytical method validation (FDA/EMA), particularly for drugs that are used at low doses or have a narrow therapeutic index. It corrects for the variability inherent in sample preparation and mass spectrometry detection.
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| Molecular Formula |
C14H22N2O2
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|---|---|
| Molecular Weight |
250.336683750153
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| Exact Mass |
256.205
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| CAS # |
194930-04-6
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| Related CAS # |
Rivastigmine;123441-03-2
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| PubChem CID |
10729795
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
18
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| Complexity |
269
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])N(C(C)C1=CC(=CC=C1)OC(=O)N(C)CC)C([2H])([2H])[2H]
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| InChi Key |
XSVMFMHYUFZWBK-LIJFRPJRSA-N
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| InChi Code |
InChI=1S/C14H22N2O2/c1-6-16(5)14(17)18-13-9-7-8-12(10-13)11(2)15(3)4/h7-11H,6H2,1-5H3/i3D3,4D3
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| Chemical Name |
[3-[1-[bis(trideuteriomethyl)amino]ethyl]phenyl] N-ethyl-N-methylcarbamate
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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 | 3.9946 mL | 19.9728 mL | 39.9457 mL | |
| 5 mM | 0.7989 mL | 3.9946 mL | 7.9891 mL | |
| 10 mM | 0.3995 mL | 1.9973 mL | 3.9946 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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