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| 1mg |
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| Other Sizes |
| Targets |
Cefotaxime-d3 acts as an antibacterial agent by targeting the same bacterial proteins as its non-deuterated parent, cefotaxime. It binds to penicillin-binding proteins (PBPs), which are transpeptidases essential for the cross-linking of the peptidoglycan layer in the bacterial cell wall. By inhibiting these PBPs, it blocks the final step of cell wall synthesis. This leads to the activation of autolytic enzymes (murein hydrolases), resulting in bacterial cell lysis and death. The mechanism is bactericidal, meaning it kills bacteria rather than just inhibiting their growth. The deuterium label does not alter the mechanism of action. It is a deuterium-labeled cefotaxime, which is a third-generation cephalosporin.
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| ln Vitro |
The in vitro activity of Cefotaxime-d3 is expected to be identical to that of unlabeled cefotaxime, although it is not directly tested as a drug. The non-labeled cefotaxime has broad-spectrum in vitro activity against a wide range of Gram-positive and Gram-negative bacteria, including many that are resistant to earlier generation cephalosporins. It is highly stable to most beta-lactamases. Typical MICs (minimum inhibitory concentrations): E. coli (0.03-0.12 microg/mL), Klebsiella spp. (0.06-0.25 microg/mL), and S. aureus (1-4 microg/mL). The deuterated version is used as an internal standard to accurately measure these MICs when conducting resistance studies, ensuring that the quantification of the drug in the test medium is precise. It is a deuterium-labeled cefotaxime, which is a beta-lactamase-stable cephalosporin.
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| ln Vivo |
Cefotaxime-d3 is not administered for in vivo activity. Its non-labeled parent, cefotaxime, is a clinically used antibiotic. Cefotaxime is indicated for the treatment of serious infections caused by susceptible bacteria, including sepsis (blood infection), meningitis, pneumonia, and gonorrhea. It is administered intravenously (IV) or intramuscularly (IM) because it is poorly absorbed orally. In vivo, it is widely distributed in body tissues and fluids, and it penetrates the blood-brain barrier, making it effective for treating bacterial meningitis. The half-life is short (about 1 hour). The D3-labeled version is used in clinical studies to accurately measure the drug concentration in patients or animals. It is a deuterium-labeled cefotaxime. Cefotaxime is a beta-lactamase-stable cephalosporin and third-generation cephalosporin antibiotic.
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| Enzyme Assay |
Non-cellular assays for Cefotaxime-d3 are analytical rather than biological. The most common protocol is a plasma protein binding assay using equilibrium dialysis combined with LC-MS/MS. A fixed concentration of cefotaxime (e.g., 10 microg/mL) is spiked into human plasma. A known amount of Cefotaxime-d3 is added as an internal standard. The plasma sample is placed in one chamber of a dialysis cell, separated by a semi-permeable membrane from a buffer chamber (PBS). The system is incubated at 37degC for 4-6 hours. After equilibration, samples are taken from both chambers. The ratio of the drug concentration in the plasma chamber vs. the buffer chamber is measured by LC-MS/MS (using the deuterated standard for quantification). This calculates the percentage of drug bound to plasma proteins. This data is essential for determining the drug's free fraction, which correlates with its therapeutic activity. It is a deuterium-labeled cefotaxime. It is a stable cephalosporin.
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| Cell Assay |
Cellular assays for Cefotaxime-d3 are not common. However, for the parent drug, cell-based assays are used to determine the post-antibiotic effect (PAE). A standard protocol uses a culture of S. aureus in Mueller-Hinton broth. The bacteria are exposed to a supratherapeutic concentration (e.g., 10x MIC) of cefotaxime for 1 hour. The antibiotic is then removed by centrifugation and washing. A control culture is treated identically but without the antibiotic. Cefotaxime-d3 can be used to ensure that the washing step was effective (i.e., to prove the absence of residual antibiotic in the supernatant by LC-MS/MS). The bacteria are re-incubated in fresh medium. The time it takes for the bacterial count to increase by 1 log10 (10-fold) is measured. The PAE is the difference in regrowth time between the treated culture and the control culture. Cefotaxime has a short PAE against Gram-positive cocci but a longer PAE against Gram-negative bacilli. It is a deuterium-labeled cefotaxime, which is a beta-lactamase-stable cephalosporin.
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| Animal Protocol |
In vivo animal experiments for cefotaxime are typically PK/PD studies. A standard protocol uses a neutropenic mouse thigh infection model. Female ICR mice are rendered neutropenic by cyclophosphamide injections. They are then infected intramuscularly in the thigh with a standardized inoculum of a test organism (e.g., E. coli). After infection, the mice are treated with cefotaxime subcutaneously at various doses (e.g., 10, 50, 200 mg/kg) and dosing intervals. Cefotaxime-d3 is not administered to the mice; it is used as a standard in the LC-MS/MS analysis of their plasma samples. Blood is collected from the mice at various time points. The plasma is analyzed using Cefotaxime-d3 as an internal standard. The bacterial burden in the thigh tissue is measured at the end of the experiment. The data is used to define the PK/PD index (e.g., %T > MIC) required for bacterial killing. This helps determine the optimal clinical dosing regimen. It is a deuterium-labeled cefotaxime. It is a deuterium-labeled internal standard.
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| ADME/Pharmacokinetics |
Cefotaxime-d3 has a molecular weight of 458.48 (for the free acid) or 480.47 (for the sodium salt). Its molecular formula is C16H14D3N5O7S2 (for the free acid). It is a white to off-white solid powder. It is soluble in DMSO (250 mg/mL) and water (moderately). It is also soluble in organic solvents like methanol. For storage, the powder should be kept at -20degC, protected from light. It is stable for 3 years in powder form. Solutions in DMSO should be stored at -80degC for up to 6 months. The compound is a beta-lactam antibiotic. As a labeled compound, its retention time in HPLC is identical to the unlabeled drug, but it has a 3 Dalton mass shift, allowing for highly specific detection. It is a stable isotope-labeled cefotaxime. Cefotaxime is a third-generation cephalosporin.
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| Toxicity/Toxicokinetics |
Cefotaxime-d3 is considered a safe chemical for handling in a laboratory environment. The parent drug, cefotaxime, has a well-established clinical safety profile, though it can cause allergic reactions (including anaphylaxis) in penicillin-allergic patients. Common side effects include injection site reactions, gastrointestinal disturbances (diarrhea), and rash. The deuterated compound is not a drug and is not intended for human consumption. However, as a beta-lactam compound, it is a potential allergen. Standard safety precautions for handling antibiotics should be observed: use of a fume hood (to avoid inhalation of fine powder), gloves, and a lab coat. In case of skin contact, wash thoroughly. It is for research use only. It is not classified as a mutagen or carcinogen in standard assays. It is a stable isotope-labeled compound. It is a third-generation cephalosporin antibiotic with broad-spectrum activity.
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| References |
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| Additional Infomation |
Cefotaxime-d3 is an essential tool in clinical pharmacology and infectious disease research. The use of stable isotope-labeled (SIL) internal standards is the gold standard for LC-MS/MS bioanalysis. The D3 label allows for the creation of a calibration curve with a very high degree of accuracy because the standard and the analyte have nearly identical physicochemical properties. They co-elute from the HPLC column, which corrects for any ion suppression or enhancement effects in the mass spectrometer. This is critical for therapeutic drug monitoring (TDM) in intensive care unit (ICU) patients, where changes in kidney function can drastically alter antibiotic levels. The use of this standard ensures that patients receive the correct dose, maximizing efficacy and minimizing the development of bacterial resistance. It is a deuterium-labeled cefotaxime, which is a beta-lactamase-stable cephalosporin and third-generation cephalosporin antibiotic with broad-spectrum activity.
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| Molecular Formula |
C16H14D3N5O7S2
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| Molecular Weight |
458.48
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| Related CAS # |
Cefotaxime;63527-52-6;Cefotaxime-d3 sodium
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| Appearance |
White to off-white solid powder
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| Synonyms |
Cefotaxim-d3; HR-756-d3
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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) |
DMSO : ~250 mg/mL (~545.28 mM; with heating and sonication)
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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 | 2.1811 mL | 10.9056 mL | 21.8112 mL | |
| 5 mM | 0.4362 mL | 2.1811 mL | 4.3622 mL | |
| 10 mM | 0.2181 mL | 1.0906 mL | 2.1811 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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