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L-Citrulline-13C (L-citrulline 13C)

Cat No.:V72466 Purity: ≥98%
L-Citrulline-13C is L-Citrulline with the 13C mark.
L-Citrulline-13C (L-citrulline 13C)
L-Citrulline-13C (L-citrulline 13C) Chemical Structure CAS No.: 94740-46-2
Product category: Endogenous Metabolite
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
Other Sizes

Other Forms of L-Citrulline-13C (L-citrulline 13C):

  • L-Citrulline-d4 (L-citrulline-d4)
  • L-Citrulline-d6
  • L-Citrulline-d2
  • L-Citrulline-CoA
Official Supplier of:
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Top Publications Citing lnvivochem Products
Product Description
L-Citrulline-13C is L-Citrulline with the 13C mark. L-Citrulline is an amino acid (AA) derived from ornithine produced during the catabolism of proline, glutamine and glutamate, or l-arginine obtained through the arginine-citrulline pathway acid.
L-Citrulline-13C (CAS: 94740-46-2) is a stable isotope-labeled analog of the amino acid L-citrulline, where the carbon atom in the ureido group is enriched with the heavy isotope carbon-13 (13C). L-Citrulline is a naturally occurring, non-proteinogenic amino acid and a key intermediate in the urea cycle. This labeled compound is used as a tracer and internal standard for studying nitrogen metabolism and the urea cycle by LC-MS.
Biological Activity I Assay Protocols (From Reference)
Targets
L-Citrulline-13C has no independent pharmacological target. The unlabeled L-citrulline is an intermediate in the urea cycle, a vital pathway for removing toxic ammonia from the body. It is produced from ornithine and carbamoyl phosphate and is converted to argininosuccinate by the enzyme argininosuccinate synthetase (ASS). This makes it a key substrate in the process of recycling nitrogen and creating the essential amino acid arginine.
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].
L-Citrulline is not directly tested for in vitro activity in most assays. However, the unlabeled form is known to modulate cellular nitrogen balance and is a precursor for arginine synthesis. It has been shown to enhance the viability and function of endothelial cells in culture by promoting the production of nitric oxide (NO). It also acts as a potent antioxidant, helping to protect cells from oxidative stress.
ln Vivo
In vivo, L-citrulline is a critical molecule for whole-body nitrogen homeostasis. It is used as a clinical biomarker of enterocyte function because it is produced in the small intestine. The 13C-labeled version is used to trace the flux of nitrogen through the urea cycle and to assess renal function. Unlabeled L-citrulline is also used as a dietary supplement to increase arginine levels and improve blood flow by boosting NO production.
Enzyme Assay
L-Citrulline-13C is used as an internal standard for LC-MS assays. A stock solution is prepared in a solvent like water or 0.1% formic acid. A known amount of this standard is spiked into a biological sample (e.g., plasma, urine, tissue homogenate) before processing. After protein precipitation or other extraction steps, the sample is analyzed by mass spectrometry. The ratio of the unlabeled L-citrulline to the L-Citrulline-13C standard is used for precise quantification.
Cell Assay
For in vitro cellular experiments, L-Citrulline-13C can be added to cell culture media as a tracer. For instance, hepatocytes or primary liver cells can be incubated with the labeled citrulline. At various time points, cells are harvested and their metabolites are extracted. The extracted samples are analyzed by LC-MS to track the 13C label as it is converted into argininosuccinate and arginine, providing real-time data on the activity of the urea cycle in a controlled environment.
Animal Protocol
For in vivo animal experiments, L-Citrulline-13C is often administered to rodents via an intraperitoneal (IP) injection or an intravenous (IV) infusion. Blood samples are collected at multiple time points before and after the administration of the tracer. The plasma is then analyzed by LC-MS to measure the appearance of the labeled citrulline and its conversion to labeled arginine. This technique, known as stable isotope tracer kinetics, is powerful for measuring organ-specific function, such as assessing renal function.
ADME/Pharmacokinetics
L-Citrulline-13C has the same pharmacokinetic (PK) properties as unlabeled L-citrulline. It is rapidly absorbed from the gut (when administered orally) and is not taken up by the liver. It is transported in the plasma and primarily cleared by the kidneys, where it is converted to arginine. Its half-life in plasma is relatively short, typically about 1-2 hours in healthy humans. This rapid clearance is due to its efficient conversion to arginine and subsequent use in protein synthesis.
Toxicity/Toxicokinetics
L-Citrulline is a naturally occurring, low-toxicity amino acid. It is generally recognized as safe (GRAS) and is a common ingredient in dietary supplements. The 13C-labeled version is chemically identical and is considered non-toxic. As an intermediate in the urea cycle, it is essential for life, and the body handles excess amounts efficiently by converting them to arginine or excreting them in the urine. No specific toxicity is associated with its use in research.
References

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

Additional Infomation
L-Citrulline-13C is not a drug but a research-use stable isotope-labeled standard and tracer. Its primary application is as an internal standard for the accurate quantification of L-citrulline in complex biological matrices like plasma and urine. It is also a powerful tool for studying the urea cycle, particularly in the context of liver disease and kidney function. Furthermore, it is used in research on nitric oxide (NO) metabolism and cardiovascular health.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
13CC5H13N3O3
Molecular Weight
176.18
Exact Mass
176.099
CAS #
94740-46-2
Related CAS #
L-Citrulline;372-75-8
PubChem CID
66575410
Appearance
White to off-white solid powder
LogP
0.638
Hydrogen Bond Donor Count
4
Hydrogen Bond Acceptor Count
4
Rotatable Bond Count
5
Heavy Atom Count
12
Complexity
171
Defined Atom Stereocenter Count
1
SMILES
C(C[C@@H](C(=O)O)N)CN[13C](=O)N
InChi Key
RHGKLRLOHDJJDR-JGTYJTGKSA-N
InChi Code
InChI=1S/C6H13N3O3/c7-4(5(10)11)2-1-3-9-6(8)12/h4H,1-3,7H2,(H,10,11)(H3,8,9,12)/t4-/m0/s1/i6+1
Chemical Name
(2S)-2-amino-5-(aminocarbonylamino)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 and light.
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: 100 mg/mL (567.60 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 5.6760 mL 28.3801 mL 56.7601 mL
5 mM 1.1352 mL 5.6760 mL 11.3520 mL
10 mM 0.5676 mL 2.8380 mL 5.6760 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

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
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?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

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:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
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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