| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
As a stable isotope-labeled internal standard, methylmalonic acid-d3 does not exert its effects through binding to specific pharmacological targets in the traditional sense. Instead, its "target" is the analytical method in which it is used as a reference standard. The compound is designed to have identical chemical properties to unlabeled methylmalonic acid but with a distinct mass due to the presence of three deuterium atoms. This allows it to co-elute with unlabeled methylmalonic acid in chromatographic separation while being distinguishable by mass spectrometry. Methylmalonic acid itself binds with coenzyme A to form methylmalonyl-CoA, a metabolic intermediate that is transformed to succinic acid by a vitamin B12-dependent catalytic step. In biological systems, elevated levels of methylmalonic acid indicate vitamin B12 deficiency or inherited metabolic disorders. The d3-labeled version of methylmalonic acid enables researchers to accurately quantify methylmalonic acid levels in biological samples, providing a tool for diagnosing vitamin B12 deficiency and monitoring metabolic disorders.
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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].
In vitro, methylmalonic acid-d3 is used as an internal standard for the quantification of methylmalonic acid in biological samples by LC-MS/MS. The compound is added to samples at known concentrations prior to sample preparation to correct for matrix effects, extraction efficiency, and instrument variability. The deuterium labeling ensures that the compound can be distinguished from endogenous methylmalonic acid in mass spectrometry-based assays, allowing for accurate quantification even in complex biological matrices. The compound is typically dissolved in appropriate solvents (e.g., methanol, water) to prepare stock and working solutions for analytical applications. In method development and validation studies, methylmalonic acid-d3 is used to assess the accuracy, precision, and robustness of analytical methods for methylmalonic acid quantification. The compound's chemical properties are identical to those of unlabeled methylmalonic acid, ensuring that it behaves identically during sample preparation and chromatographic separation. This makes methylmalonic acid-d3 an ideal internal standard for quantitative analysis of methylmalonic acid in a variety of biological matrices including serum, plasma, and urine. |
| ln Vivo |
In vivo, methylmalonic acid-d3 enables precise tracking of methylmalonic acid metabolism and B12 status assessment. Following administration to animals or humans, the compound can be detected in biological fluids using mass spectrometry, allowing researchers to study the metabolism and excretion of methylmalonic acid. The deuterium label ensures that the administered compound can be distinguished from endogenous methylmalonic acid, enabling accurate pharmacokinetic and metabolic studies. Methylmalonic acid is a clinical biomarker of functional vitamin B12 status. Elevated levels of methylmalonic acid indicate vitamin B12 deficiency or inherited metabolic disorders. The d3-labeled version of methylmalonic acid can be used to study the kinetics of methylmalonic acid metabolism and the factors that influence its levels in the body. In clinical research, methylmalonic acid-d3 may be used in stable isotope tracer studies to assess vitamin B12 status and metabolic function.
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| Enzyme Assay |
In vitro enzyme assays for methylmalonic acid-d3 are not typically performed, as the compound is primarily used as an analytical standard. However, the compound can be used in enzymatic assays to study the activity of enzymes involved in methylmalonic acid metabolism, such as methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA in a vitamin B12-dependent reaction. In these assays, methylmalonyl-CoA is incubated with methylmalonyl-CoA mutase and adenosylcobalamin (vitamin B12), and the formation of succinyl-CoA is measured. Methylmalonic acid-d3 can be used as an internal standard to quantify the formation of methylmalonic acid from methylmalonyl-CoA in coupled assays. The compound's chemical properties are identical to those of unlabeled methylmalonic acid, ensuring that it behaves identically in biochemical assays.
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| Cell Assay |
In vitro cell-based experiments with methylmalonic acid-d3 involve adding the labeled compound to cell culture media and studying its uptake and metabolism. Cells are cultured in standard growth media, and methylmalonic acid-d3 is added at various concentrations for varying periods. Following incubation, cells and culture media are collected, and metabolites are extracted using appropriate methods. The extracts are then analyzed by LC-MS/MS to measure the deuterium-labeled methylmalonic acid and its metabolites. This allows researchers to quantify methylmalonic acid uptake, metabolism, and excretion in cell models. In studies of vitamin B12 metabolism, methylmalonic acid-d3 can be used to assess the functional status of vitamin B12-dependent pathways. Cell viability is routinely monitored to ensure that the labeled compound does not affect cell health. Each experiment includes appropriate controls (unlabeled cells, vehicle controls) and is performed in triplicate to ensure statistical reliability.
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| Animal Protocol |
In vivo animal experiments with methylmalonic acid-d3 involve administration of the labeled compound to animals followed by collection of biological samples for mass spectrometry analysis. The compound is typically administered via oral gavage, intraperitoneal injection, or intravenous infusion at doses ranging from 1-100 mg/kg. Following administration, blood samples are collected at various time points (typically 0, 0.5, 1, 2, 4, 8, 12, 24 hours) to measure the appearance and disappearance of labeled methylmalonic acid in the circulation. Urine samples are also collected to study the excretion of methylmalonic acid and its metabolites. At the end of the experiment, animals are euthanized, and tissues (liver, kidney) are collected for analysis. Metabolites are extracted from plasma, urine, and tissues, and the deuterium enrichment of methylmalonic acid and its metabolites is measured by LC-MS/MS. This allows researchers to quantify methylmalonic acid metabolism in different organs and tissues, assess the impact of disease states on methylmalonic acid homeostasis, and evaluate the effects of pharmacological interventions. All animal procedures are conducted in accordance with institutional animal care and use committee guidelines, with appropriate sample sizes (typically n=4-6 per group) to ensure statistical power.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of methylmalonic acid-d3 are studied using the isotope label to track the absorption, distribution, metabolism, and excretion of methylmalonic acid. Following oral or intravenous administration, the compound is rapidly absorbed and distributed to tissues. The deuterium label allows for the specific detection of administered methylmalonic acid in biological samples without interference from endogenous unlabeled methylmalonic acid. Pharmacokinetic parameters such as half-life, volume of distribution, clearance, and bioavailability can be calculated from the concentration-time profiles of labeled methylmalonic acid in plasma and urine. Methylmalonic acid is a dicarboxylic acid that is primarily metabolized through the vitamin B12-dependent conversion of methylmalonyl-CoA to succinyl-CoA. The labeled compound enables precise tracking of these metabolic processes. The pharmacokinetics of methylmalonic acid-d3 are expected to be similar to those of unlabeled methylmalonic acid, with rapid distribution and elimination.
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| Toxicity/Toxicokinetics |
The toxicological profile of methylmalonic acid-d3 is consistent with that of unlabeled methylmalonic acid, an endogenous metabolite that is present in the body at low concentrations. Methylmalonic acid is a normal metabolic intermediate that can accumulate in vitamin B12 deficiency. High levels of methylmalonic acid are associated with metabolic acidosis and neurological damage. However, the compound is generally considered safe at the low concentrations used in analytical applications. The deuterium label is a stable isotope that does not impart any additional toxicity to the compound. The compound is supplied as a high-purity research chemical for laboratory use only and is not intended for human consumption. Standard safety precautions should be observed when handling the compound, including the use of appropriate personal protective equipment. The compound should be stored in a cool, dry place, away from light and moisture. As with all chemicals, ingestion, inhalation, and skin contact should be avoided.
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| References | |
| Additional Infomation |
Methylmalonic acid-d3 is a valuable research tool for clinical diagnostics, metabolic studies, and vitamin B12 research. It is used as an internal standard for the quantification of methylmalonic acid in biological samples by LC-MS/MS. Methylmalonic acid binds with coenzyme A to form methylmalonyl-CoA, a metabolic intermediate that is transformed to succinic acid by a vitamin B12-dependent catalytic step. The compound is broadly used as a clinical biomarker of functional vitamin B12 status. Methylmalonic acid is an indicator of vitamin B-12 deficiency in cancer patients. The d3-labeled version of methylmalonic acid has the molecular formula C₄H₃D₃O₄ and a molecular weight of 121.11 g/mol. It is not a drug and is not approved for any clinical indication. It is strictly for research use only. Its high purity and isotopic enrichment ensure accurate and reproducible results in analytical applications. Methylmalonic acid-d3 is an essential tool for diagnosing vitamin B12 deficiency and monitoring metabolic disorders.
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| Molecular Formula |
C4H3D3O4
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|---|---|
| Molecular Weight |
121.11
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| Exact Mass |
121.045
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| CAS # |
42522-59-8
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| Related CAS # |
Methylmalonic acid;516-05-2
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| PubChem CID |
10820511
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
334.4±25.0 °C at 760 mmHg
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| Melting Point |
134-136ºC(lit.)
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| Flash Point |
170.2±19.7 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.474
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| LogP |
-0.21
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
8
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| Complexity |
103
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])C(C(=O)O)C(=O)O
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| InChi Key |
ZIYVHBGGAOATLY-FIBGUPNXSA-N
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| InChi Code |
InChI=1S/C4H6O4/c1-2(3(5)6)4(7)8/h2H,1H3,(H,5,6)(H,7,8)/i1D3
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| Chemical Name |
2-(trideuteriomethyl)propanedioic 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) |
DMSO: 100 mg/mL (825.70 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (20.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (20.64 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (20.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 8.2570 mL | 41.2848 mL | 82.5696 mL | |
| 5 mM | 1.6514 mL | 8.2570 mL | 16.5139 mL | |
| 10 mM | 0.8257 mL | 4.1285 mL | 8.2570 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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