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SDMA-d6 (Symmetric dimethylarginine-d6; NG,NG'-Dimethyl-L-arginine-d6)

Cat No.:V82247 Purity: ≥98%
SDMA-d6 is the deuterium labelled form of SDMA.
SDMA-d6 (Symmetric dimethylarginine-d6; NG,NG'-Dimethyl-L-arginine-d6)
SDMA-d6 (Symmetric dimethylarginine-d6; NG,NG'-Dimethyl-L-arginine-d6) Chemical Structure CAS No.: 1331888-08-4
Product category: Keap1-Nrf2
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
1mg
5mg
Other Sizes

Other Forms of SDMA-d6 (Symmetric dimethylarginine-d6; NG,NG'-Dimethyl-L-arginine-d6):

  • SDMA (p-hydroxyazobenzene-p′-sulfonate)
  • DSDMA
  • SDMA
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Top Publications Citing lnvivochem Products
Product Description
SDMA-d6 is the deuterium labelled form of SDMA. SDMA (Symmetric dimethylarginine) is an endogenous inhibitor of nitric oxide (NO) synthase activity.
SDMA-d6 (Symmetric dimethylarginine-d6; NG,NG'-Dimethyl-L-arginine-d6; CAS#: 1331888-08-4) is a stable isotope-labeled compound where six hydrogen atoms are replaced with deuterium. It is intended for use as an internal standard for the quantification of symmetric dimethylarginine (SDMA) by mass spectrometry in biological samples.
Biological Activity I Assay Protocols (From Reference)
Targets
No direct pharmacological target; SDMA-d6 is an isotope-labeled internal standard for mass spectrometry. The unlabeled compound, symmetric dimethylarginine (SDMA), is an endogenous inhibitor of nitric oxide synthase (NOS) activity and serves as a biomarker for renal function. SDMA is formed by the methylation of arginine by methyltransferases (PRMT5 and PRMT7) and is excreted primarily by the kidneys.
ln Vitro
In the process of developing new drugs, stable heavy isotopes of carbon, hydrogen, and other elements have been added to pharmacological molecules, mostly as quantitative tracers. Due to its potential effects on medication pharmacokinetics and metabolic properties, deuteration is a matter for worry [1].
As a deuterated internal standard, SDMA-d6 is not biologically active. The unlabeled compound, SDMA (symmetric dimethylarginine), is an endogenous metabolite that competes with L-arginine for nitric oxide synthase (NOS) and inhibits NOS activity (IC50 ~ 10-50 uM). Elevated SDMA levels in chronic kidney disease are associated with increased cardiovascular risk and inflammation. SDMA also acts as a pro-inflammatory agent, promoting the release of TNF-alpha, IL-6, and IL-8 from monocytes and macrophages. SDMA inhibits cellular L-arginine uptake and reduces NO production in endothelial cells, contributing to endothelial dysfunction.
ln Vivo
No direct in vivo activity for SDMA-d6. The unlabeled SDMA is involved in the pathogenesis of chronic kidney disease (CKD), cardiovascular disease, and inflammation. In animal models, chronic SDMA infusion (3 mg/kg/day for 6 weeks via osmotic minipump) in C57BL/6 mice induces glomerular filtration rate (GFR) reduction, increased systemic vascular resistance, myocardial dysfunction, and renal fibrosis. SDMA is considered a sensitive marker for early detection of CKD, as its levels rise earlier than creatinine in some patient populations.
Enzyme Assay
No specific enzyme/receptor binding protocols for SDMA-d6. For quantification of SDMA in biological samples by LC-MS/MS: (1) Prepare calibration standards in blank serum/plasma or urine by spiking known concentrations of unlabeled SDMA (analyte) with a fixed concentration of SDMA-d6 (internal standard, typically 50-500 ng/mL). (2) Protein precipitation: add 3-5 volumes of acetonitrile or methanol containing 0.1% formic acid to 50-100 uL of sample, vortex, centrifuge at 14,000 rpm for 10 min. (3) Alternatively, use solid-phase extraction (SPE) on cation-exchange cartridges for cleaner extracts. (4) Evaporate supernatant to dryness, reconstitute in mobile phase (e.g., 0.1% formic acid in water/acetonitrile, 95:5). (5) Separate on a hydrophilic interaction liquid chromatography (HILIC) column (e.g., ZIC-HILIC 2.1 × 100 mm, 3.5 um) at 40degC with a gradient elution. (6) Detect by ESI-MS/MS in positive ion mode using MRM transitions: SDMA: 203 → 172 (or 203 → 70); SDMA-d6: 209 → 178 (or 209 → 76). (7) Calculate analyte concentration using the analyte/internal standard peak area ratio.
Cell Assay
(1) Seed human umbilical vein endothelial cells (HUVECs) or monocytes (THP-1) in culture medium. (2) For isotope tracing: add SDMA-d6 (0.1-10 uM) to cell culture medium for 0-24 h. (3) Collect cells and culture supernatant, extract metabolites, and analyze by LC-MS/MS to study SDMA metabolism and cellular uptake. (4) For functional studies using unlabeled SDMA: treat HUVECs with SDMA (10-100 uM) for 24-72 h, measure NO production (using DAF-FM DA fluorescent probe), eNOS phosphorylation (Western blot), and cell viability (MTT). (5) For inflammation studies: treat THP-1 cells with SDMA (10-100 uM) for 6-24 h, measure TNF-alpha, IL-6, and IL-8 by ELISA.
Animal Protocol
(1) For chronic kidney disease models: use male Sprague-Dawley rats (250-300 g) or C57BL/6 mice (20-25 g) with 5/6 nephrectomy or adenine diet (0.25% adenine in chow for 4 weeks) to induce CKD. (2) Collect plasma and urine samples at baseline and throughout disease progression. (3) To each 50 uL of plasma or urine sample, add 20 uL of SDMA-d6 internal standard solution (1-10 ug/mL in water). (4) Perform protein precipitation and LC-MS/MS analysis as described above. (5) Quantify SDMA levels in samples using calibration curves. (6) Correlate SDMA levels with serum creatinine, BUN, and GFR to assess kidney function. (7) For exogenous SDMA infusion studies: implant osmotic minipumps delivering SDMA (3 mg/kg/day) subcutaneously into mice for 6 weeks, collect blood and urine weekly, and analyze SDMA levels by LC-MS/MS with SDMA-d6 as internal standard.
ADME/Pharmacokinetics
Standard formulation for SDMA-d6 as internal standard: prepare a stock solution in water or 50% methanol/water at 1 mg/mL, store at -20degC protected from light. For LC-MS analysis, dilute stock solution to working concentration of 0.5-5 ug/mL in 0.1% formic acid in water. The compound is soluble in water (125 mg/mL, 600 mM). For in vitro studies: dissolve unlabeled SDMA in PBS or cell culture medium at 10-100 mM stock, filter sterilize (0.22 um). SDMA-d6 is chemically stable at -20degC for 3 years (powder) and at -80degC for 6 months (in solution). Avoid repeated freeze-thaw cycles (max 3 cycles).
Toxicity/Toxicokinetics
SDMA-d6 is considered non-toxic as it is a stable isotope-labeled endogenous metabolite. The unlabeled SDMA is an endogenous compound present in plasma at normal levels (0.3-0.8 uM in healthy humans; levels rise to 1-5 uM in CKD). In vitro: CCK-8 assay on HUVECs with unlabeled SDMA (10-1000 uM) shows IC50 > 200 uM for 48 h. In vivo toxicity: in mice, chronic infusion of SDMA (3 mg/kg/day for 6 weeks) causes no overt toxicity but induces renal fibrosis and reduced GFR; MTD for acute SDMA administration (IP) > 100 mg/kg. The isotope-labeled version is for research use only, not for human therapeutic use.
References

[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.

[2]. Symmetrical dimethylarginine: a new combined parameter for renal function and extent ofcoronary artery disease.

[3]. Symmetric dimethylarginine as a proinflammatory agent in chronic kidney disease.Clin J Am Soc Nephrol. 2011 Oct;6(10):2374-83.

[4]. Symmetric Dimethylarginine Assay Validation, Stability, and Evaluation as a Marker for the EarlyDetection of Chronic Kidney Disease in Dogs. J Vet Intern Med. 2015 Jul-Aug;29(4):1036-44.

[5]. Effects of chronic SDMA infusion on glomerular filtration rate, blood pressure, myocardial function and renal histology in C57BL6/J mice. Nephrol Dial Transplant. 2013 Jun;28(6):1434-9.

Additional Infomation
SDMA-d6 is a high-purity stable isotope-labeled internal standard (≥95% purity) used for the accurate quantification of symmetric dimethylarginine (SDMA) in biological samples by GC-MS or LC-MS. SDMA is an endogenous methylated arginine derivative and a sensitive biomarker for renal function, particularly in chronic kidney disease (CKD). Unlike asymmetric dimethylarginine (ADMA), which inhibits NOS, SDMA is not a direct NOS inhibitor but has been shown to induce inflammatory responses and is associated with cardiovascular morbidity and mortality. This product is not a drug and is not FDA-approved; it is strictly for research use in clinical chemistry, biomarker discovery, and analytical method development.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C8H18N4O2
Molecular Weight
208.291091442108
Exact Mass
208.18
CAS #
1331888-08-4
Related CAS #
SDMA;30344-00-4
PubChem CID
136259133
Appearance
Colorless to off-white solid-liquid Mixture
LogP
-3.7
Hydrogen Bond Donor Count
4
Hydrogen Bond Acceptor Count
4
Rotatable Bond Count
7
Heavy Atom Count
14
Complexity
206
Defined Atom Stereocenter Count
1
SMILES
OC([C@H](CCCN/C(=N/C([2H])([2H])[2H])/NC([2H])([2H])[2H])N)=O
InChi Key
HVPFXCBJHIIJGS-BGUMHVNPSA-N
InChi Code
InChI=1S/C8H18N4O2/c1-10-8(11-2)12-5-3-4-6(9)7(13)14/h6H,3-5,9H2,1-2H3,(H,13,14)(H2,10,11,12)/t6-/m0/s1/i1D3,2D3
Chemical Name
(2S)-2-amino-5-[[N,N'-bis(trideuteriomethyl)carbamimidoyl]amino]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

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), 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)
Solubility Data
Solubility (In Vitro)
H2O :~125 mg/mL (~600.12 mM)
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
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*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 : PEG300Tween 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).
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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL 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).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 4.8010 mL 24.0050 mL 48.0100 mL
5 mM 0.9602 mL 4.8010 mL 9.6020 mL
10 mM 0.4801 mL 2.4005 mL 4.8010 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.

Calculator

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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