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DL-Homocystine-3,3,3',3',4,4,4',4'-d8

Cat No.:V72492 Purity: ≥98%
DL-Homocystine-3,3,3',3',4,4,4',4'-d8 is the deuterated form of DL-Homocystine.
DL-Homocystine-3,3,3',3',4,4,4',4'-d8
DL-Homocystine-3,3,3',3',4,4,4',4'-d8 Chemical Structure CAS No.: 108641-82-3
Product category: Endogenous Metabolite
This product is for research use only, not for human use. We do not sell to patients.
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Other Forms of DL-Homocystine-3,3,3',3',4,4,4',4'-d8:

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Top Publications Citing lnvivochem Products
Product Description
DL-Homocystine-3,3,3',3',4,4,4',4'-d8 is the deuterated form of DL-Homocystine. DL-Homocystine is made up of two molecules of homocysteine, which is believed to play an important role in the pathogenesis and pathophysiology of schizophrenia.
DL-Homocystine-3,3,3',3',4,4,4',4'-d8 (CAS: 108641-82-3) is the deuterium-labeled (d8) form of DL-Homocystine, the disulfide-linked dimer of the non-proteinogenic amino acid homocysteine. In this stable isotope-labeled analog, eight specific hydrogen atoms at positions 3 and 4 on both cysteine units are replaced with deuterium. It is used as an analytical standard and a tracer to study homocysteine metabolism with high precision by mass spectrometry.
Biological Activity I Assay Protocols (From Reference)
Targets
DL-Homocystine-d8 has no pharmacological target. The unlabeled DL-Homocystine is a biological molecule that is the oxidized form of homocysteine, a key intermediate in the methionine cycle. Elevated levels of homocysteine (and consequently homocystine) are a risk factor for cardiovascular disease, neurodegenerative disorders, and schizophrenia. Its role is as a toxic metabolite and a diagnostic biomarker, not as a ligand for a beneficial drug target.
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].
As a stable isotope standard, DL-Homocystine-d8 is not used to measure in vitro activity. The unlabeled DL-Homocystine is used in cell culture to induce cellular stress. It has been shown to cause endothelial dysfunction, promote the generation of reactive oxygen species, and induce apoptosis in neuronal cell cultures. These effects are associated with hyperhomocysteinemia, a condition linked to various age-related diseases.
ln Vivo
In vivo, DL-Homocystine itself is a disulfide present in plasma. Its concentration is a direct reflection of the plasma homocysteine level, as these two rapidly interconvert via thiol-disulfide exchange reactions. It is not a therapeutic agent but a biomarker. The d8-labeled version is used to track the metabolism of homocysteine. Abnormal levels are linked to the pathogenesis of cardiovascular and psychiatric conditions.
Enzyme Assay
For in vitro assays, DL-Homocystine-d8 is typically dissolved in a suitable solvent like 0.1% formic acid or water to prepare a stock solution. It is used as an internal standard for LC-MS or GC-MS. A fixed amount of the standard is spiked into a biological sample (e.g., plasma, tissue homogenate). After sample preparation steps like protein precipitation, the sample is analyzed by mass spectrometry. The signal ratio allows for precise quantification of homocystine/homocysteine.
Cell Assay
For in vitro cell-based studies, DL-Homocystine-d8 can be added to cell culture media as a tracer. Cells are grown in the presence of the labeled compound. After a certain period, the cells are harvested, and the metabolites are extracted. The extracted samples are analyzed by LC-MS to track how the label from homocystine is incorporated into downstream metabolites of the methionine cycle, such as methionine or S-adenosylmethionine (SAM).
Animal Protocol
For in vivo animal experiments, DL-Homocystine-d8 can be administered as a tracer to study homocysteine metabolism. The compound is typically given to rodents via an intravenous (IV) bolus or a bolus followed by a continuous infusion. Blood samples are collected at multiple time points. The plasma is analyzed by mass spectrometry to measure the enrichment of the labeled homocysteine over time, allowing researchers to calculate whole-body homocysteine turnover and clearance rates.
ADME/Pharmacokinetics
DL-Homocystine-d8 is a tracer and shares the same pharmacokinetics as unlabeled homocystine. Homocysteine is a small, thiol-containing amino acid. Its plasma half-life is short, on the order of minutes to a few hours. It is rapidly cleared by the kidneys and the liver, where it can be remethylated back to methionine or transsulfurated to cysteine. Its levels are a dynamic balance between production and clearance.
Toxicity/Toxicokinetics
Homocysteine is a naturally occurring, low-level metabolite. However, at elevated concentrations (hyperhomocysteinemia), it is considered a toxic agent and is a well-established, independent risk factor for cardiovascular disease, stroke, and cognitive impairment. The d8-labeled version is chemically identical and should be handled as a potential biohazard. For research use, standard laboratory safety precautions are adequate.
References

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

[2]. Homocysteine and schizophrenia: from prenatal to adult life. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Sep;29(7):1175-80.

Additional Infomation
DL-Homocystine-d8 is not a drug but a deuterium-labeled stable isotope internal standard. It is extensively used in clinical research and diagnostics for the accurate measurement of total homocysteine (tHcy) levels in blood plasma, which is a crucial test for assessing cardiovascular risk and diagnosing inborn errors of methionine metabolism. It is also a vital tool for metabolic research to study the methionine cycle and the pathological effects of hyperhomocysteinemia.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C8H8D8N2O4S2
Molecular Weight
276.40
Exact Mass
276.105
CAS #
108641-82-3
Related CAS #
DL-Homocystine;870-93-9
PubChem CID
11265862
Appearance
White to off-white solid powder
Density
1.4±0.1 g/cm3
Boiling Point
507.6±50.0 °C at 760 mmHg
Flash Point
260.8±30.1 °C
Vapour Pressure
0.0±2.8 mmHg at 25°C
Index of Refraction
1.619
LogP
1.03
Hydrogen Bond Donor Count
4
Hydrogen Bond Acceptor Count
8
Rotatable Bond Count
9
Heavy Atom Count
16
Complexity
216
Defined Atom Stereocenter Count
0
SMILES
[2H]C([2H])(C(C(=O)O)N)C([2H])([2H])SSC([2H])([2H])C([2H])([2H])C(C(=O)O)N
InChi Key
ZTVZLYBCZNMWCF-SVYQBANQSA-N
InChi Code
InChI=1S/C8H16N2O4S2/c9-5(7(11)12)1-3-15-16-4-2-6(10)8(13)14/h5-6H,1-4,9-10H2,(H,11,12)(H,13,14)/i1D2,2D2,3D2,4D2
Chemical Name
2-amino-4-[(3-amino-3-carboxy-1,1,2,2-tetradeuteriopropyl)disulfanyl]-3,3,4,4-tetradeuteriobutanoic 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)
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
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 3.6179 mL 18.0897 mL 36.1795 mL
5 mM 0.7236 mL 3.6179 mL 7.2359 mL
10 mM 0.3618 mL 1.8090 mL 3.6179 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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  • Enter 10 in the Concentration box and choose the correct unit (mM)
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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.

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:
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  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
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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:
  • 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.

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  • 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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