| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
HIV-1
alpha-Lipoic Acid-d5 is a stable isotope-labeled compound that acts as an internal standard. Its non-labeled counterpart, alpha-Lipoic Acid (Thioctic Acid), is an essential cofactor for five mitochondrial enzyme systems: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, branched-chain alpha-keto acid dehydrogenase, glycine cleavage system, and the alpha-ketoacid dehydrogenase complex. These enzymes are critical for the decarboxylation of alpha-keto acids and the production of acetyl-CoA. Additionally, alpha-Lipoic Acid exerts potent antioxidant effects by directly scavenging reactive oxygen species (ROS), chelating metal ions, and regenerating endogenous antioxidants such as vitamins C and E, and glutathione (GSH). It also activates the transcription factor Nrf2, leading to the upregulation of phase II detoxifying enzymes. alpha-Lipoic Acid-d5 mimics these biological targets for analytical purposes. |
|---|---|
| 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 in vitro activity of alpha-Lipoic Acid-d5 is expected to be identical to that of the non-labeled alpha-Lipoic Acid (ALA). ALA is a potent antioxidant that has been shown to directly scavenge a variety of reactive oxygen species (ROS) including superoxide radicals, hydroxyl radicals, and hypochlorous acid. In cultured cell lines (e.g., HepG2 liver cancer cells, SH-SY5Y neuronal cells), ALA treatment (0.1-1 mM) significantly reduces levels of lipid peroxidation and protein carbonylation induced by oxidative stressors. Furthermore, ALA has been demonstrated to induce apoptosis in cancer cells via the activation of endoplasmic reticulum stress (ERS) pathways and to inhibit NF-kappaB activation. In hepatocytes, ALA (50-250 uM) has been shown to improve insulin sensitivity and increase cellular glucose uptake. The labeled version, ALA-d5, is used as an internal standard to accurately quantify ALA concentrations in these in vitro systems. |
| ln Vivo |
alpha-Lipoic Acid-d5 is a stable isotope-labeled compound used as an internal standard. The in vivo activity of its non-labeled parent compound, alpha-Lipoic Acid (ALA), is well-documented. In rodent models of diabetes, oral or intraperitoneal administration of ALA (50-200 mg/kg) significantly lowers blood glucose levels and improves insulin sensitivity. This is primarily attributed to its ability to activate AMP-activated protein kinase (AMPK) in skeletal muscle and liver. In models of diabetic neuropathy, ALA has been shown to reduce oxidative stress and improve nerve conduction velocity. Additionally, in animal models of neurodegeneration (Alzheimer‘s and Parkinson's), ALA crosses the blood-brain barrier and exerts neuroprotective effects by reducing amyloid-beta aggregation, improving mitochondrial function, and reducing neuroinflammation. ALA-d5 is used as an internal standard in these studies to accurately quantify ALA and its metabolites in plasma and tissues.
|
| Enzyme Assay |
A generic non-cell-based assay for alpha-Lipoic Acid-d5 involves evaluating its antioxidant capacity using a chemical assay. The most common is the DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay. Prepare a 0.1 mM solution of DPPH in methanol (protect from light). Prepare a stock solution of unlabeled alpha-Lipoic Acid in ethanol and then dilute with water to obtain working concentrations ranging from 1 uM to 1 mM. Add 100 uL of each alpha-Lipoic Acid concentration to 100 uL of DPPH solution in a 96-well plate. Include a control containing 100 uL of water and 100 uL of DPPH, and a blank containing 100 uL of water and 100 uL of methanol. Cover the plate and incubate it in the dark at room temperature for 30 minutes. Measure the absorbance at 517 nm using a microplate reader. Calculate the percentage of inhibition using the formula: [(A_control - A_sample) / A_control] × 100. Determine the IC₅0 value from the dose-response curve. Use alpha-Lipoic Acid-d5 as an LC-MS internal standard to validate the true concentration of ALA in the assay.
|
| Cell Assay |
A standard in vitro cell-based assay for alpha-Lipoic Acid-d5 utilizes HepG2 human liver cancer cells. Maintain HepG2 cells in DMEM supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin at 37degC in a 5% CO2 incubator. Seed the cells at a density of 1×10⁴ cells/well in 96-well plates and allow them to attach overnight. Pre-treat the cells with varying concentrations of unlabeled alpha-Lipoic Acid (50-500 uM) for 12-24 hours. Then, expose the cells to an oxidative stressor such as 0.5 mM H2O2 (hydrogen peroxide) for 4 hours. After treatment, assess cell viability using the MTT assay. Add 10 uL of MTT reagent (5 mg/mL) to each well, incubate for 3 hours, then remove the medium and add 100 uL of DMSO to dissolve the formazan crystals. Measure the absorbance at 570 nm. Use alpha-Lipoic Acid-d5 as an internal standard in an LC-MS analysis of the culture medium to accurately determine the precise concentration of alpha-Lipoic Acid that the cells were exposed to during the experiment.
|
| Animal Protocol |
A typical in vivo protocol for the unlabeled alpha-Lipoic Acid (ALA) uses a rat model of diabetes induced by streptozotocin (STZ). First, induce diabetes in male Wistar rats (180-220 g) via a single intraperitoneal injection of STZ (60 mg/kg) dissolved in 0.1 M citrate buffer (pH 4.5). After 72 hours, confirm hyperglycemia (blood glucose >250 mg/dL). Divide the diabetic rats into groups (n=6-8): diabetic control (vehicle), and treatment groups receiving unlabeled ALA (25, 50, or 100 mg/kg) intraperitoneally once daily for 4 weeks. Include a non-diabetic control group. At the end of the treatment period, collect blood samples for serum isolation and sacrifice the animals to collect sciatic nerves, liver, and kidney tissue. Analyze the collected plasma and tissues for oxidative stress markers (MDA, GSH, SOD). Use alpha-Lipoic Acid-d5 as the internal standard in an LC-MS/MS analysis of these samples to accurately quantify the levels of ALA and its metabolites.
|
| ADME/Pharmacokinetics |
The pharmacokinetic profile of alpha-Lipoic Acid-d5 is expected to be identical to that of its non-labeled counterpart, alpha-Lipoic Acid (ALA). In humans, ALA is rapidly absorbed after oral administration, but it has low oral bioavailability (approx. 30%) due to extensive first-pass metabolism in the liver. The elimination half-life (t½) is approximately 20-40 minutes. The compound is rapidly distributed and has a volume of distribution of approximately 450 mL/kg. Protein binding is moderate (approx. 80%). ALA undergoes extensive metabolism via side-chain oxidation and reduction, forming various metabolites including bisnorlipoic acid, tetranorlipoic acid, and their corresponding reduced forms. These metabolites are primarily excreted in the urine. The labeled ALA-d5 is used as an internal standard for LC-MS-based PK studies to provide more accurate estimates of these parameters by correcting for matrix effects and extraction efficiency.
|
| Toxicity/Toxicokinetics |
The toxicity of alpha-Lipoic Acid-d5 itself is not well-characterized, but it is generally considered safe for handling at low concentrations for analytical purposes. The unlabeled alpha-Lipoic Acid (ALA) is generally regarded as safe (GRAS) for use as a dietary supplement. The oral LD₅0 for ALA is >2000 mg/kg in rats, indicating low acute toxicity. The primary adverse effects observed in humans at high doses (above 600 mg/day) are mild gastrointestinal issues such as nausea and stomach upset. ALA has also been associated with rare cases of insulin autoimmune syndrome (IAS), leading to hypoglycemia. No significant genotoxicity or carcinogenicity has been reported in standard assays. For researchers, standard laboratory safety precautions such as wearing gloves and goggles should be employed when handling this compound. It should be stored in a tightly closed container in a cool, dry place.
|
| References | |
| Additional Infomation |
alpha-Lipoic Acid-d5 is the stable isotope-labeled (deuterated) version of alpha-Lipoic Acid (Thioctic acid). Its primary application is as an internal standard for the precise quantitation of alpha-Lipoic Acid in biological matrices (plasma, urine, tissues) using LC-MS/MS. This application is critical for pharmacokinetic studies, bioavailability assessments, and metabolism research. The non-labeled alpha-Lipoic Acid is a naturally occurring compound synthesized in the human body and found in foods like spinach, broccoli, and red meat. It is an essential cofactor for mitochondrial enzyme complexes involved in energy metabolism. It is also widely used as a dietary supplement for its antioxidant properties, particularly for conditions like diabetic neuropathy and metabolic syndrome. Research continues on its potential benefits in cardiovascular disease and neurodegenerative disorders like Alzheimer‘s and Parkinson's disease.
|
| Molecular Formula |
C8H9D5O2S2
|
|---|---|
| Molecular Weight |
211.36
|
| Exact Mass |
211.075
|
| CAS # |
1189471-66-6
|
| PubChem CID |
46782067
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
2.785
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
12
|
| Complexity |
150
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
[2H]C1(CSSC1([2H])C([2H])([2H])CCCC(=O)O)[2H]
|
| InChi Key |
AGBQKNBQESQNJD-KEDGJJNOSA-N
|
| InChi Code |
InChI=1S/C8H14O2S2/c9-8(10)4-2-1-3-7-5-6-11-12-7/h7H,1-6H2,(H,9,10)/i3D2,5D2,7D
|
| Chemical Name |
5,5-dideuterio-5-(3,4,4-trideuteriodithiolan-3-yl)pentanoic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 4.7313 mL | 23.6563 mL | 47.3126 mL | |
| 5 mM | 0.9463 mL | 4.7313 mL | 9.4625 mL | |
| 10 mM | 0.4731 mL | 2.3656 mL | 4.7313 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
