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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Nε,Nε,Nε-Trimethyllysine-d9 chloride is not a direct enzyme inhibitor or receptor agonist. Instead, the non-labeled form of this compound is a naturally occurring modified amino acid that serves as a metabolic precursor. It is derived from lysine through post-translational methylation of the ε-amino group. It is a substrate for gut microbial enzymes that convert it to trimethylamine (TMA) and subsequently to trimethylamine N-oxide (TMAO), or to TMAVA. The physiological target is the gut microbial metabolic pathway. TMAVA has been shown to inhibit fatty acid oxidation. The compound is not a drug and is used primarily as an internal standard. The deuterated form is used for quantification in metabolomics studies.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
No specific in vitro activity data is provided for this compound because it is an internal standard. The biological activity of non-labeled Nε,Nε,Nε-Trimethyllysine has been studied in the context of carnitine biosynthesis and gut microbiota metabolism. Nε,Nε,Nε-Trimethyllysine is an intermediate in the endogenous synthesis of carnitine from lysine. In the gut, it is metabolized by the microbiota to form TMAVA. TMAVA has been shown to inhibit fatty acid oxidation and may contribute to the pathogenesis of metabolic diseases. In cell-based assays, TMAVA (0.1-1 mM) reduces fatty acid oxidation in hepatocytes and cardiomyocytes, leading to lipid accumulation. Nε,Nε,Nε-Trimethyllysine itself is not directly cytotoxic. |
| ln Vivo |
No specific in vivo data is provided for this deuterated compound. The in vivo metabolism of Nε,Nε,Nε-Trimethyllysine has been studied in animal models. Oral administration of labeled Nε,Nε,Nε-Trimethyllysine to mice leads to its conversion to TMAVA by gut microbiota, which can be detected in plasma and urine. Germ-free mice show minimal conversion, confirming the role of gut flora. TMAVA levels in plasma correlate with dietary intake and are associated with metabolic disorders in humans. The deuterated internal standard is used for accurate quantification of endogenous Nε,Nε,Nε-Trimethyllysine in these studies. The parent compound is a precursor for TMAVA.
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| Enzyme Assay |
Nε,Nε,Nε-Trimethyllysine-d9 chloride is not used in cell-free assays for target engagement. It is used as an internal standard in analytical chemistry. For LC-MS/MS method validation, calibration standards are prepared by spiking known concentrations of non-labeled Nε,Nε,Nε-Trimethyllysine chloride into blank biological matrix (e.g., human plasma, mouse plasma, or urine). A fixed concentration of Nε,Nε,Nε-Trimethyllysine-d9 chloride (e.g., 50-500 ng/mL) is added to each calibrator, QC sample, and study sample. Samples are prepared by protein precipitation with acetonitrile or methanol containing the internal standard, or by solid-phase extraction (SPE). After centrifugation, the supernatant is injected onto a hydrophilic interaction chromatography (HILIC) or reversed-phase C18 column coupled to a triple quadrupole mass spectrometer. Detection is performed in positive ion electrospray mode (ESI+). MRM transitions: parent compound m/z 189.2 → m/z 84.1; internal standard m/z 198.2 → m/z 93.1 (for d9). The peak area ratio is used for quantification.
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| Cell Assay |
The compound is not typically used in cellular assays. For studies of carnitine biosynthesis or gut microbiota metabolism, cell culture models are not appropriate because the conversion of trimethyllysine to TMAVA requires gut bacteria. Human colon carcinoma cell lines (e.g., Caco-2) or primary human intestinal epithelial cells may be used to study the absorption of trimethyllysine. In a typical absorption assay, Caco-2 cells are grown on transwell inserts for 21 days to form polarized monolayers. Nε,Nε,Nε-Trimethyllysine chloride (1-100 microM) is added to the apical chamber, and samples are collected from the basolateral chamber at various time points (0.5-4 hours). The concentration of the compound in the basolateral chamber is measured by LC-MS/MS using the deuterated internal standard. Apparent permeability (Papp) is calculated. This method is used to assess intestinal absorption.
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| Animal Protocol |
The deuterated internal standard is used for the quantification of trimethyllysine in animal studies. In a typical mouse study, male C57BL/6 mice (6-8 weeks) are fed a control diet or a high-fat diet for 12 weeks. At the end of the feeding period, blood is collected by cardiac puncture, plasma is separated, and urine is collected. Tissues (liver, kidney, cecum content) are collected and snap-frozen. Nε,Nε,Nε-Trimethyllysine levels in plasma, urine, and tissue homogenates are quantified by LC-MS/MS using Nε,Nε,Nε-Trimethyllysine-d9 chloride as internal standard. For pharmacokinetic studies, mice receive an oral gavage of non-labeled Nε,Nε,Nε-Trimethyllysine chloride (e.g., 10-100 mg/kg) in saline. Blood is collected at multiple time points (0-24 hours), and the concentration of the compound and its metabolite (TMAVA) are measured by LC-MS/MS using the deuterated internal standards. This helps to understand the absorption, distribution, and metabolism of trimethyllysine.
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| ADME/Pharmacokinetics |
Nε,Nε,Nε-Trimethyllysine-d9 chloride has a molecular formula of C9H12D9ClN2O2 and a molecular weight of 233.78 g/mol. The lyophilized powder should be stored at -20degC in a sealed container, protected from moisture, where it is stable for up to 3 years. For solution storage, stock solutions in water or methanol should be stored at -80degC for up to 6 months. The compound is soluble in water (10-20 mg/mL) and methanol. For analytical use, working solutions are prepared by dilution in water or mobile phase (e.g., acetonitrile/water with 0.1% formic acid). The internal standard is typically added to samples at a concentration of 50-500 ng/mL. The product is a stable isotope-labeled internal standard for research use only.
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| Toxicity/Toxicokinetics |
This product is for research use only and is not for human therapeutic use. No specific toxicity data is available for the deuterated form. The non-labeled compound Nε,Nε,Nε-Trimethyllysine is a naturally occurring amino acid derivative and is considered safe at concentrations typically found in biological systems. The deuterated internal standard is used at minute quantities (ng/mL levels) that pose negligible risk. Standard laboratory safety practices (gloves, lab coat, safety glasses) should be followed. Avoid inhalation of powder. The compound is not a drug. It is intended for use as an internal standard in research applications only.
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| References |
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.
[2]. Zhao M, et al. TMAVA, a Metabolite of Intestinal Microbes, Is Increased in Plasma From Patients With Liver Steatosis, Inhibits γ-Butyrobetaine Hydroxylase, and Exacerbates Fatty Liver in Mice. Gastroenterology. 2020;158(8):2266-2281.e27. |
| Additional Infomation |
Trimethyllysine (TML) is a post-translationally modified amino acid. It is an intermediate in the carnitine biosynthesis pathway and is also produced from dietary proteins. In recent years, TML has gained attention as a potential biomarker for cardiovascular disease and metabolic disorders. It is converted by gut microbiota to trimethylamine (TMA), which is further oxidized by the liver to trimethylamine N-oxide (TMAO), a compound associated with atherosclerosis. TML can also be converted to TMAVA, which inhibits fatty acid oxidation. Nε,Nε,Nε-Trimethyllysine-d9 chloride is a stable isotope-labeled internal standard for the accurate quantification of TML by mass spectrometry. This product is not a drug and is for research use only. Supplier information must not be included.
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| Molecular Formula |
C9H12D9CLN2O2
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| Appearance |
White to off-white solid powder
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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.) |
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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