| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Malic acid-d3 has no independent pharmacological target as a stable isotope tracer. The unlabeled malic acid is a dicarboxylic acid that plays a crucial role in many sour or tart foods and is an important intermediate in the tricarboxylic acid (TCA) cycle (also known as the Krebs cycle), a central pathway for cellular respiration and energy production. Malic acid is also involved in the malate-aspartate shuttle, which transfers reducing equivalents across the mitochondrial membrane.
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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 tracer, Malic acid-d3 is not tested for classical in vitro pharmacological activity. In cell culture studies, it is used to trace malic acid metabolism through the TCA cycle and malate-aspartate shuttle. The deuterated form allows for precise quantification of metabolic processes via mass spectrometry and NMR spectroscopy, providing insights into enzymatic activities and energy production mechanisms without interfering with normal cellular metabolism. |
| ln Vivo |
Malic acid-d3 has no in vivo pharmacological activity as a therapeutic agent. It is used in animal studies as a stable isotope tracer to investigate TCA cycle activity, energy metabolism, and malate-aspartate shuttle function in various tissues including liver, heart, and skeletal muscle. The deuterium-labeled compound can be administered intravenously or orally and tracked by LC-MS or NMR to study metabolic fluxes and pathway regulation under various physiological and pathological conditions.
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| Enzyme Assay |
For in vitro tracer experiments, Malic acid-d3 is dissolved in an appropriate solvent (e.g., DMSO, water, or 0.1% formic acid) to prepare a stock solution (e.g., 10-100 mM). The compound is then added to cell culture media (typically 10-500 uM) or biochemical reaction mixtures. For TCA cycle studies, cells are incubated with Malic acid-d3 for labeling periods of 0-24 hours. Metabolites are extracted with methanol:water (80:20) or 0.1% formic acid in methanol, centrifuged, and analyzed by LC-MS/MS to trace the incorporation of deuterium into malate, oxaloacetate, citrate, and other TCA cycle intermediates.
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| Cell Assay |
For cell-based studies, cells (e.g., hepatocytes, cardiomyocytes, or cancer cell lines) are cultured in standard medium (DMEM with 10% FBS, 2 mM glutamine). After reaching appropriate confluence, the medium is replaced with medium containing Malic acid-d3 at a defined concentration (e.g., 10-500 uM). Cells are incubated for 1-48 hours at 37degC in 5% CO2. At each time point, cells are washed with PBS and lysed in 0.1% formic acid in methanol. After protein precipitation by centrifugation (10,000-15,000 rpm, 10 minutes), the supernatant is analyzed by LC-MS/MS to quantify deuterated malate and its TCA cycle metabolites (e.g., fumarate, succinate, citrate, oxaloacetate).
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| Animal Protocol |
For in vivo tracer studies, Malic acid-d3 is administered to rodents via intravenous injection, intraperitoneal injection (e.g., 10-100 mg/kg), or oral gavage. Blood samples are collected at multiple time points (e.g., 0, 15, 30, 60, 120, 240 minutes). At terminal time points, tissues (liver, heart, kidney, skeletal muscle) are harvested, snap-frozen in liquid nitrogen, and stored at -80degC. Tissues are homogenized in 0.1% formic acid in methanol, centrifuged, and analyzed by LC-MS/MS to quantify deuterated malic acid and TCA cycle intermediates. For NMR-based metabolic flux analysis, tissue extracts are analyzed by ¹3C-NMR or 2H-NMR.
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| ADME/Pharmacokinetics |
Malic acid-d3 is a stable isotope tracer and follows the same ADME properties as natural malic acid. Malic acid is rapidly absorbed from the gastrointestinal tract, distributed to all tissues, and enters the TCA cycle. It is metabolized to oxaloacetate by malate dehydrogenase (MDH), producing NADH for oxidative phosphorylation. In humans, plasma malic acid levels are low (1-10 uM) and the compound has a short half-life (10-30 minutes) due to rapid TCA cycle turnover. The deuterated version is used to calibrate analytical methods and does not alter the ADME properties of the endogenous metabolite.
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| Toxicity/Toxicokinetics |
Malic acid is a naturally occurring dicarboxylic acid with low toxicity (GRAS status). The LD50 in rodents is >2,000 mg/kg. At high doses, malic acid may cause gastrointestinal disturbances including diarrhea and abdominal discomfort. The deuterated version is chemically identical except for isotopic substitution and exhibits the same safety profile. Standard laboratory safety precautions for handling organic acids apply. Not intended for human consumption.
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| References | |
| Additional Infomation |
Malic acid-d3 is not a drug but a deuterium-labeled stable isotope tracer. It has no approved therapeutic status, no clinical trial history as a therapeutic agent, and is not intended for human consumption. This compound is used for research applications including metabolic tracer studies to trace the TCA cycle and malate-aspartate shuttle, NMR spectroscopy to study reaction mechanisms and molecular structures, and as an internal standard for LC-MS or GC-MS quantification of malic acid in biological samples. It is also used to help elucidate enzyme mechanisms within the TCA cycle and for pharmaceutical development studies. Available with >98% purity and ≥98 atom% D. Solubility: H2O 100 mg/mL (729.34 mM), DMSO 100 mg/mL.
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| Molecular Formula |
C4H3D3O5
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|---|---|
| Molecular Weight |
137.11
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| Exact Mass |
137.04
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| CAS # |
104596-63-6
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| Related CAS # |
Malic acid;6915-15-7
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| PubChem CID |
71309504
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
306.4±27.0 °C at 760 mmHg
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| Flash Point |
153.4±20.2 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.529
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| LogP |
-1.26
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
9
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| Complexity |
129
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])(C(=O)O)C([2H])(C(=O)O)O
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| InChi Key |
BJEPYKJPYRNKOW-FUDHJZNOSA-N
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| InChi Code |
InChI=1S/C4H6O5/c5-2(4(8)9)1-3(6)7/h2,5H,1H2,(H,6,7)(H,8,9)/i1D2,2D
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| Chemical Name |
2,2,3-trideuterio-3-hydroxybutanedioic acid
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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 | 7.2934 mL | 36.4671 mL | 72.9341 mL | |
| 5 mM | 1.4587 mL | 7.2934 mL | 14.5868 mL | |
| 10 mM | 0.7293 mL | 3.6467 mL | 7.2934 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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