| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Hydroxy Itraconazole-d8 targets the same enzyme as its parent drug, itraconazole: cytochrome P450 14alpha-demethylase (CYP51, also known as sterol 14alpha-demethylase) in fungal cells. By inhibiting this enzyme, itraconazole and its active metabolite block the synthesis of ergosterol, an essential component of the fungal cell membrane, leading to increased membrane permeability and fungal cell death. Hydroxyitraconazole is considered equipotent to itraconazole.
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| ln Vitro |
Hydroxy Itraconazole-d8 is not typically used in cell-free enzyme assays as it serves as an analytical standard. However, unlabeled hydroxyitraconazole can be evaluated for CYP51 inhibition. In cell-free assays, purified fungal CYP51 is incubated with a substrate (e.g., lanosterol) and NADPH in the presence of varying concentrations of hydroxyitraconazole. The decrease in ergosterol production or accumulation of 14alpha-methylated sterols is measured by LC-MS/MS. The labeled version is used for quantification.
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| ln Vivo |
Hydroxyitraconazole (unlabeled) exhibits antifungal activity against a broad range of fungal pathogens, including Candida, Aspergillus, and Cryptococcus species. In broth microdilution assays, the minimum inhibitory concentration (MIC) of hydroxyitraconazole is comparable to that of itraconazole. The compound is fungistatic, inhibiting fungal growth through ergosterol depletion. Hydroxy Itraconazole-d8 is not used in these activity assays.
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| Enzyme Assay |
The antifungal activity of unlabeled hydroxyitraconazole is determined using a broth microdilution method according to CLSI guidelines. Serial dilutions of the compound (0.03-16 microg/mL) are prepared in RPMI-1640 medium. Fungal inoculum (e.g., C. albicans, A. fumigatus) is added, and plates are incubated at 35degC for 24-48 hours. The MIC is defined as the lowest concentration that prevents visible growth. Hydroxy Itraconazole-d8 is used as an internal standard for drug quantification in these assays by LC-MS/MS.
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| Cell Assay |
For in vitro cell culture experiments, human hepatocytes or liver microsomes are incubated with itraconazole (1-10 microM) for specified time points (0-24 hours). Hydroxyitraconazole production is quantified by LC-MS/MS using Hydroxy Itraconazole-d8 as the internal standard. The compound is also used in metabolic stability studies to assess CYP3A4-mediated itraconazole metabolism. In fungal cell culture, hydroxyitraconazole uptake and ergosterol content are measured using LC-MS/MS.
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| Animal Protocol |
In animal studies, Hydroxy Itraconazole-d8 is not used as a therapeutic agent but as an internal standard. Itraconazole is administered orally (10-50 mg/kg) in rodent models of systemic fungal infection (e.g., C. albicans disseminated infection). Blood and tissue samples are collected at various time points, and levels of itraconazole and its hydroxy metabolite are quantified by LC-MS/MS using the d8-labeled compound as the internal standard. Efficacy is assessed by fungal burden and survival.
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| ADME/Pharmacokinetics |
Itraconazole exhibits highly variable and dose-dependent oral absorption, requiring an acidic gastric environment. It is extensively metabolized by CYP3A4 to hydroxyitraconazole, which is the major active metabolite. Hydroxyitraconazole reaches peak plasma concentrations 2-5 hours after itraconazole administration and has a longer half-life (15-25 hours) than itraconazole (20-30 hours). The d8-labeled compound is used for accurate quantification of the metabolite in PK studies.
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| Toxicity/Toxicokinetics |
Hydroxy Itraconazole-d8 is used in trace amounts as an analytical standard and does not contribute to toxicity. The unlabeled parent itraconazole has a well-established safety profile. Common adverse effects include gastrointestinal disturbances (nausea, vomiting, diarrhea), hepatotoxicity (elevated liver enzymes), and skin rashes. Potentially serious adverse effects include congestive heart failure, peripheral edema, and drug-drug interactions via CYP3A4 inhibition. The d8 label does not alter the toxicity profile.
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| Additional Infomation |
Itraconazole is an FDA-approved triazole antifungal drug used for the treatment of various systemic and superficial fungal infections, including blastomycosis, histoplasmosis, aspergillosis, and onychomycosis. Hydroxyitraconazole is its major active metabolite. Hydroxy Itraconazole-d8 is a research-grade stable isotope-labeled compound used exclusively as an internal standard for method development and bioanalysis in drug metabolism and pharmacokinetic studies.
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| Molecular Formula |
C35H30D8CL2N8O5
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|---|---|
| Molecular Weight |
729.68
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| Related CAS # |
Hydroxy Itraconazole;112559-91-8;Itraconazole;84625-61-6
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| Appearance |
White to off-white 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 | 1.3705 mL | 6.8523 mL | 13.7046 mL | |
| 5 mM | 0.2741 mL | 1.3705 mL | 2.7409 mL | |
| 10 mM | 0.1370 mL | 0.6852 mL | 1.3705 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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