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Myristoyl-L-carnitine-d3 chloride is a stable isotope-labeled internal standard. Its unlabeled parent, myristoyl-L-carnitine, is a long-chain acylcarnitine species formed by the conjugation of myristic acid (a 14-carbon saturated fatty acid) with carnitine via carnitine acyltransferase. This compound is involved in the transport of long-chain fatty acids across the inner mitochondrial membrane for beta-oxidation. The molecular target of acylcarnitines is the carnitine palmitoyltransferase (CPT) system: CPT1 converts fatty acyl-CoA to acylcarnitine on the outer mitochondrial membrane, and CPT2 reconverts it to fatty acyl-CoA on the inner membrane for beta-oxidation. Elevated plasma myristoyl-L-carnitine is a biomarker for impaired fatty acid oxidation. The labeled version is used to accurately quantify this biomarker. Myristoyl-L-carnitine also acts as a signaling molecule, activating the NLRP3 inflammasome at high concentrations.
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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 in vitro biological activity of Myristoyl-L-carnitine-d3 chloride is not independently studied, as it is an internal standard. Its unlabeled parent, myristoyl-L-carnitine, has been shown to possess pro-inflammatory activity. In cultured human THP-1 macrophages, myristoyl-L-carnitine (10-100 uM) activates the NLRP3 inflammasome, leading to caspase-1 activation and IL-1beta secretion. This effect is dependent on the length of the acyl chain; long-chain acylcarnitines like myristoyl-L-carnitine (C14) are potent activators, while short-chain species are less active. In isolated rat cardiac mitochondria, myristoyl-L-carnitine (50-500 uM) acts as a substrate for beta-oxidation, increasing oxygen consumption and ATP production. At high concentrations (>200 uM), it can also disrupt mitochondrial membrane potential and induce swelling. The labeled myristoyl-L-carnitine-d3 is used as an internal standard in LC-MS to accurately quantify acylcarnitine species in cell culture media and cell lysates. |
| ln Vivo |
The in vivo activity of Myristoyl-L-carnitine-d3 chloride is not directly evaluated; it is used as an internal standard. Its unlabeled parent, myristoyl-L-carnitine, is an endogenous acylcarnitine that circulates in plasma at concentrations of approximately 0.05-0.2 uM in healthy individuals. In patients with fatty acid oxidation disorders, such as very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and carnitine palmitoyltransferase (CPT) deficiency, myristoyl-L-carnitine levels are markedly elevated (up to 10-50 uM) and serve as a sensitive diagnostic biomarker. In mouse models of high-fat diet-induced obesity and insulin resistance, plasma myristoyl-L-carnitine levels are increased and correlate with markers of inflammation. Myristoyl-L-carnitine-d3 is used as a stable isotope-labeled internal standard for the accurate quantification of acylcarnitine species in plasma, dried blood spots, and urine for diagnostic and research purposes.
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| Enzyme Assay |
A generic non-cell-based assay for Myristoyl-L-carnitine-d3 chloride involves its use as an internal standard in an LC-MS/MS method for acylcarnitine analysis in dried blood spots (DBS). Prepare a standard stock solution of unlabeled myristoyl-L-carnitine in methanol (1 mg/mL). Prepare a separate stock solution of the internal standard Myristoyl-L-carnitine-d3 at the same concentration. Prepare calibration standards by spiking the unlabeled analyte into a blank matrix (e.g., washed red blood cell extract or synthetic blood on filter paper) to achieve concentrations ranging from 0.1 to 50 uM. Add a fixed concentration of the internal standard (e.g., 5 uM) to each calibration standard. For sample preparation, punch a 3.2 mm disc from a dried blood spot sample directly into a 96-well plate. Add 100 uL of extraction solution (methanol containing internal standard) and incubate for 30 minutes at room temperature with shaking. Transfer the extract to a new plate and evaporate under nitrogen. Reconstitute in 150 uL of mobile phase. Analyze by LC-MS/MS in positive ion mode with multiple reaction monitoring (MRM). Monitor the mass transitions: m/z 400.3 → 85.1 for myristoyl-L-carnitine (the carnitine-specific product ion from neutral loss of trimethylamine), and m/z 403.3 → 85.1 for the myristoyl-L-carnitine-d3 internal standard (with identical fragmentation). Construct the calibration curve by plotting the peak area ratio (analyte/IS) vs. the nominal concentration.
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| Cell Assay |
A standard in vitro cell-based protocol for the unlabeled myristoyl-L-carnitine is used to study fatty acid oxidation in human fibroblasts. Culture human dermal fibroblasts from healthy controls and patients with suspected fatty acid oxidation disorders in DMEM supplemented with 10% FBS and 1% penicillin/streptomycin at 37degC in a 5% CO2 incubator. Seed cells in 6-well plates at 5×10⁵ cells/well and allow to reach confluence (typically 4-5 days). The day before the assay, replace the medium with FBS-free DMEM to standardize conditions. On the day of the assay, wash cells twice with PBS and add 1 mL of reaction buffer containing 0.5% fatty acid-free BSA, 0.5 mM L-carnitine, and 100 uM of unlabeled myristoyl-L-carnitine (or C14 fatty acid plus carnitine). Incubate at 37degC for 2-4 hours. To measure beta-oxidation, collect the culture medium and assay for the production of 3H2O if using radiolabeled [9,10-3H]myristate, or quantify the consumption of myristoyl-L-carnitine and production of shorter-chain acylcarnitines by LC-MS/MS using Myristoyl-L-carnitine-d3 as internal standard. Also measure the activity of CPT1 and CPT2 in cell lysates using a spectrophotometric assay.
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| Animal Protocol |
An in vivo animal protocol for Myristoyl-L-carnitine-d3 chloride is used in a mouse model of high-fat diet-induced obesity. Use male C57BL/6J mice (6 weeks old, n = 10-12 per group). Feed one group a high-fat diet (45-60% calories from fat) and the control group a standard chow diet for 12-16 weeks. At the end of the feeding period, fast mice overnight (12-14 hours). Collect blood samples via tail vein or retro-orbital puncture into EDTA tubes. Centrifuge to obtain plasma. For acylcarnitine analysis, dilute plasma (10 uL) with 90 uL of methanol containing a panel of stable isotope-labeled acylcarnitine internal standards, including Myristoyl-L-carnitine-d3 chloride. Centrifuge at 12,000g for 10 minutes to precipitate proteins. Transfer the supernatant to an autosampler vial and analyze by LC-MS/MS using a targeted acylcarnitine panel. Quantify myristoyl-L-carnitine and other acylcarnitine species (C2, C4, C6, C8, C10, C12, C14:1, C16, C18). Correlate acylcarnitine levels with body weight, fasting glucose, insulin resistance (HOMA-IR), and inflammatory markers (IL-6, TNF-alpha) to assess the relationship between fatty acid oxidation dysfunction and obesity-related metabolic disease.
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| ADME/Pharmacokinetics |
Myristoyl-L-carnitine-d3 chloride is an analytical internal standard, so its PK is the same as its unlabeled parent. Myristoyl-L-carnitine is an endogenous acylcarnitine that is produced and metabolized within cells and does not undergo classical pharmacokinetics as an administered drug. In humans, plasma levels of myristoyl-L-carnitine typically range from 0.05 to 0.2 uM in healthy, fasted individuals. The half-life of circulating acylcarnitines is approximately 30-60 minutes. Myristoyl-L-carnitine is produced in mitochondria via CPT1-mediated transfer of myristoyl-CoA (derived from fatty acid beta-oxidation or activation of free myristic acid) to carnitine. The compound is then transported into the mitochondrial matrix via the carnitine-acylcarnitine translocase (CACT) and reconverted to myristoyl-CoA by CPT2 for continued beta-oxidation. In fatty acid oxidation disorders, such as VLCAD deficiency, myristoyl-L-carnitine accumulates and is released into the bloodstream and excreted in urine (excretion rate ~0.1-1 ug/g creatinine). The labeled standard is essential for accurate quantification of this biomarker in mass spectrometry-based assays for newborn screening and clinical diagnosis.
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| Toxicity/Toxicokinetics |
Myristoyl-L-carnitine-d3 chloride is a stable isotope-labeled research compound, not a pharmaceutical drug. Its unlabeled parent, myristoyl-L-carnitine, is an endogenous acylcarnitine that is generally considered non-toxic at normal physiological concentrations. However, at pathologically elevated levels (e.g., in fatty acid oxidation disorders such as VLCAD, LCHAD, and CPT2 deficiencies, where levels can exceed 10-50 uM), long-chain acylcarnitines including myristoyl-L-carnitine are believed to contribute to the clinical manifestations of these disorders, including hypoketotic hypoglycemia, cardiomyopathy, rhabdomyolysis, and sudden death. Proposed mechanisms include disruption of mitochondrial membrane potential, inhibition of the electron transport chain, activation of the NLRP3 inflammasome, and cardiac arrhythmias due to calcium dysregulation. No specific toxicity has been reported for the labeled deuterated form. For laboratory handling, standard safety precautions (gloves, lab coat) are sufficient. The compound should be stored at -20degC, protected from light and moisture, and solutions should be stored at -80degC for long-term stability.
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| References | |
| Additional Infomation |
Myristoyl-L-carnitine-d3 chloride is the stable isotope-labeled (deuterated) version of myristoyl-L-carnitine, a long-chain acylcarnitine (C14:0) that serves as an intermediate in the transport of long-chain fatty acids into the mitochondrial matrix for beta-oxidation. It is intended for research use as an internal standard for the accurate quantification of myristoyl-L-carnitine and other acylcarnitine species in biological samples by LC-MS/MS. Myristoyl-L-carnitine is a critical diagnostic biomarker for several inborn errors of fatty acid metabolism, including very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, and carnitine palmitoyltransferase (CPT) deficiencies. Elevated levels of myristoyl-L-carnitine in newborn dried blood spots are used in newborn screening programs worldwide to identify infants at risk for these potentially fatal disorders. For research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C21H39D3CLNO4
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| Molecular Weight |
411.03
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| Exact Mass |
410.299
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| CAS # |
1334532-25-0
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| Related CAS # |
Myristoyl-L-carnitine chloride;173686-73-2
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| PubChem CID |
131872268
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
27
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| Complexity |
377
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| Defined Atom Stereocenter Count |
1
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| SMILES |
[2H]C([2H])([2H])[N+](C)(C)C[C@@H](CC(=O)O)OC(=O)CCCCCCCCCCCCC.[Cl-]
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| InChi Key |
TWGWHMYOGIGWDM-IQDJPGLDSA-N
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| InChi Code |
InChI=1S/C21H41NO4.ClH/c1-5-6-7-8-9-10-11-12-13-14-15-16-21(25)26-19(17-20(23)24)18-22(2,3)4;/h19H,5-18H2,1-4H3;1H/t19-;/m1./s1/i2D3;
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| Chemical Name |
[(2R)-3-carboxy-2-tetradecanoyloxypropyl]-dimethyl-(trideuteriomethyl)azanium;chloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 | 2.4329 mL | 12.1646 mL | 24.3291 mL | |
| 5 mM | 0.4866 mL | 2.4329 mL | 4.8658 mL | |
| 10 mM | 0.2433 mL | 1.2165 mL | 2.4329 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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