| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
The non‑deuterated parent compound alkylates DNA at O⁶‑ and N⁷‑positions of guanine, leading to crosslinking of DNA strands and inhibition of DNA replication and transcription. The nitrosourea group decomposes under physiological conditions to form an alkylating intermediate and a carbamoylating species. The deuterated version acts as a stable isotope tracer for quantitative LC‑MS analysis, enabling accurate measurement of parent drug levels in biological samples.
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| ln Vitro |
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs labeled with deuterium suggest that these compounds may offer some advantages when compared with their nondeuterated counterparts. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. Deutetrabenazine is the first deuterated drug to receive Food and Drug Administration approval. This deuterated form of the drug tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools.[1]
In vitro, the deuterated compound is used as an internal standard in LC‑MS assays for the quantification of lomustine, carmustine, and other chloroethyl nitrosoureas. It is added to biological samples (plasma, urine, tissue homogenates) at a known concentration (e.g., 10-100 ng/mL) prior to sample preparation. The compound is chemically identical to the analyte of interest except for the isotopic mass shift, allowing for accurate correction for matrix effects, extraction efficiency, and ionization suppression/enhancement. |
| ln Vivo |
Deuterated compounds may, in some cases, offer advantages over nondeuterated forms, often through alterations in clearance. Deuteration may also redirect metabolic pathways in directions that reduce toxicities. The approval of additional deuterated compounds may soon follow. Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities.
The deuterated compound is not administered to animals as a drug. It is used as an analytical standard in pharmacokinetic studies. In a typical study, the non‑deuterated lomustine (10-20 mg/kg) is administered orally to rats. Blood samples are collected over 24-72 h. The stable isotope-labeled compound (e.g., 20 ng/mL) is added to each plasma sample as an internal standard. Concentrations of lomustine are determined by LC‑MS/MS. This ensures accurate quantification of the drug, which can then be used to calculate PK parameters (Cmax, Tmax, t1/2, AUC). |
| Enzyme Assay |
The LC‑MS/MS method for quantification uses the deuterated compound as an internal standard. The analyte and internal standard are extracted from plasma by protein precipitation (acetonitrile), liquid‑liquid extraction (ethyl acetate), or solid‑phase extraction. Separation is performed on a C18 reversed‑phase column with a mobile phase of water:acetonitrile (30:70) containing 0.1% formic acid. Detection is in positive ion electrospray ionization (ESI+) mode with multiple reaction monitoring (MRM) at appropriate mass transitions for both the analyte and the internal standard. The deuterium label allows the internal standard to co‑elute with the analyte while being distinguished by mass.
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| Cell Assay |
No cell‑based assays are performed with the deuterated compound. For cell‑based studies, the non‑deuterated nitrosourea drug is used. Cells (e.g., glioma cell lines) are treated with the drug (1-100 uM) for 24-72 h. Cell viability is assessed by MTT assay. DNA damage is measured by comet assay or gamma‑H2AX immunofluorescence. Apoptosis is assessed by flow cytometry using Annexin V‑FITC/propidium iodide staining. The deuterated compound is not added to live cells.
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| Animal Protocol |
The deuterated compound is not administered to animals. In a pharmacokinetic study, male Sprague‑Dawley rats (n=6 per time point) are administered lomustine (20 mg/kg) orally or intraperitoneally. Blood samples (200 uL) are collected from the tail vein at pre‑dose and at 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h post‑dose. Plasma is separated by centrifugation. A fixed amount of the deuterated internal standard (e.g., 50 uL of 100 ng/mL solution) is added to each sample. Concentrations are determined by LC‑MS/MS, and PK parameters are calculated using non‑compartmental analysis.
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| ADME/Pharmacokinetics |
The deuterated compound is stored as a solution in methanol or acetonitrile at −20degC, protected from light. It is stable for at least 2 years under these conditions. The molecular weight is increased by 4 Da compared to the non‑deuterated parent compound due to the incorporation of four deuterium atoms (2H). The compound is chemically stable under standard storage conditions but should be handled with caution as nitrosoureas are known to be carcinogenic and mutagenic.
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| Toxicity/Toxicokinetics |
The deuterated compound is a labeled analogue of a genotoxic alkylating agent. Chloroethyl nitrosoureas are classified as carcinogenic (IARC Group 2A, probably carcinogenic to humans). They are genotoxic, inducing DNA crosslinks and mutations. The deuterated compound should be handled with extreme caution: use in a designated carcinogen hood, wear double gloves, safety goggles, and a lab coat. Avoid inhalation, skin contact, and ingestion. Decontaminate all surfaces with 2% sodium thiosulfate (which neutralizes nitrosoureas). The compound is not for human or animal therapeutic use.
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| References | |
| Additional Infomation |
The deuterated compound is not a drug; it is an analytical standard for research use only. It is used as an internal standard for the quantification of lomustine (CCNU), carmustine (BCNU), and other chloroethyl nitrosoureas in biological samples by LC‑MS/MS. This supports pharmacokinetic studies, bioequivalence studies, and therapeutic drug monitoring in cancer research. It is not intended for use as a therapeutic agent. The compound is available from specialized chemical suppliers as a stable isotope‑labeled standard.
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| Molecular Formula |
C9H12D4CLN3O3
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|---|---|
| Molecular Weight |
253.72
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| Appearance |
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 |
| 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 | 3.9414 mL | 19.7068 mL | 39.4135 mL | |
| 5 mM | 0.7883 mL | 3.9414 mL | 7.8827 mL | |
| 10 mM | 0.3941 mL | 1.9707 mL | 3.9414 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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