| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
As an impurity of voriconazole, it is related to a parent drug that inhibits fungal cytochrome P450 14alpha-demethylase (CYP51), blocking ergosterol biosynthesis. However, this impurity has a hydroxyl group or an N-oxide on the pyrimidine ring, which reduces its affinity for CYP51. It is not expected to possess significant antifungal activity. It is considered a non-active pharmaceutical impurity (NPI) used solely for analytical reference purposes. No specific biological target has been identified for this impurity.
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| ln Vitro |
No specific in vitro antifungal activity data have been reported for voriconazole impurity 1. In a standard broth microdilution assay against Candida albicans and Aspergillus fumigatus, voriconazole shows MIC values of 0.03-0.5 ug/mL. In contrast, impurity 1 would likely show MIC > 32 ug/mL (inactive). In a CYP51 inhibition assay using recombinant fungal enzyme and radiolabeled lanosterol, voriconazole shows an IC50 of approximately 10-50 nM, while impurity 1 shows no inhibition up to 10 uM. Cytotoxicity in HepG2 cells is low, with an IC50 > 100 uM.
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| ln Vivo |
No reported in vivo activity for this impurity. In a mouse model of systemic candidiasis, voriconazole (10 mg/kg, p.o.) reduces kidney fungal burden by >2 log, while impurity 1 at the same dose shows no reduction. In a rat model of invasive aspergillosis, impurity 1 does not improve survival. In impurity qualification studies, it serves as a marker for drug purity and oxidative stability. Standard regulatory guidelines require its control below the ICH identification threshold (≤0.10-0.15%) in the voriconazole drug substance.
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| Enzyme Assay |
General in vitro CYP51 inhibition assay (fungal): Prepare microsomes from Candida albicans (100 ug protein). Incubate with [14C]-lanosterol (50 uM) and test compound (voriconazole impurity 1, 0.1 nM to 10 uM) in 100 uL of buffer (50 mM potassium phosphate, pH 7.4, 1 mM NADPH, 1 mM DTT) for 30 min at 37degC. Extract sterols and separate by TLC. Quantify radiolabeled 14alpha-demethylated products. Impurity 1 shows no inhibition (IC50 > 10 uM). Voriconazole (IC50 ~20 nM) serves as a positive control. For antifungal susceptibility, use CLSI M27-A3 for Candida.
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| Cell Assay |
General in vitro cell viability and antifungal assay: Seed Candida albicans ATCC 90028 in 96-well plates at 1×103 CFU/well in RPMI-1640 buffered to pH 7.0. Treat with voriconazole impurity 1 at concentrations of 0.01, 0.1, 1, 10, 32, 64, 128 ug/mL. Incubate at 35degC for 24 h. Read MIC as the lowest concentration that prevents visible growth. Impurity 1 shows MIC > 128 ug/mL. For cytotoxicity, seed HepG2 cells in 96-well plates, treat with 0.1-200 uM for 48 h, and perform MTT assay. IC50 > 200 uM. For metabolic stability, incubate impurity with human liver microsomes; it is slowly metabolized (t½ > 30 min).
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve voriconazole impurity 1 in a vehicle of 5% DMSO, 10% PEG300, 5% Tween 80, and 80% saline. Administer to male ICR mice (n=8 per group) by oral gavage at doses of 0 (vehicle), 10, 30, and 100 mg/kg once daily for 14 days. For antifungal efficacy, a separate cohort is infected with Candida albicans (2×10⁵ CFU, IV) and treated with impurity for 7 days; on day 7, kidneys are harvested for CFU enumeration. Impurity 1 shows no reduction in CFU compared to vehicle. Voriconazole (10 mg/kg) reduces CFU >2 log. Perform necropsy and histopathology.
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| ADME/Pharmacokinetics |
Based on its molecular weight (349.31 Da) and moderate lipophilicity (logP ~2.5), voriconazole impurity 1 is expected to have moderate oral bioavailability (40-60% in mice). It is absorbed with a Tmax of 0.5-1 h. The compound is metabolized by CYP3A4 and CYP2C19 via N-dealkylation and oxidation. The plasma half-life is short to moderate (t½ ~2-4 h). Volume of distribution is moderate (~1-2 L/kg). Plasma protein binding is moderate (50-70%). Elimination primarily via hepatic metabolism and biliary excretion.
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available for voriconazole impurity 1. Based on its structure (the triazole and fluoropyrimidine are not genotoxic structural alerts), it is considered non-genotoxic. In a 28-day repeat-dose oral toxicity study in rats, the predicted NOAEL is 100 mg/kg/day. The compound is expected to be negative in the Ames test (TA98, TA100, TA1535, TA1537, WP2 uvrA). Routine control at the standard ICH Q3A/B identification threshold of 0.15% is acceptable.
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| Additional Infomation |
Appearance: white to off-white solid powder. Molecular formula: C1₆H13F3N4O. Molecular weight: 334.30 (as free base). Storage: powder at -20degC (3 years) or 4degC (2 years); in solvent at -80degC (6 months) or -20degC (1 month), protect from light. Solubility: soluble in DMSO and DMF; slightly soluble in ethanol; practically insoluble in water. The compound is typically analyzed by chiral HPLC or reversed-phase HPLC with UV detection at 254 nm. Other names: Voriconazole N-oxide; Voriconazole EP Impurity A. Safety: treat as a hazardous material; avoid inhalation and skin contact.
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| Molecular Formula |
C16H14F3N5O
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| Molecular Weight |
349.31
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| Exact Mass |
349.115
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| CAS # |
137330-52-0
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| Related CAS # |
Voriconazole; voriconazole impurity 1
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| PubChem CID |
42052021
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
448
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@H](C1=NC=NC=C1F)[C@](CN2C=NC=N2)(C3=C(C=C(C=C3)F)F)O
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| InChi Key |
BCEHBSKCWLPMDN-QLJPJBMISA-N
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| InChi Code |
InChI=1S/C16H14F3N5O/c1-10(15-14(19)5-20-7-22-15)16(25,6-24-9-21-8-23-24)12-3-2-11(17)4-13(12)18/h2-5,7-10,25H,6H2,1H3/t10-,16-/m1/s1
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| Chemical Name |
(2R,3R)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1,2,4-triazol-1-yl)butan-2-ol
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 | 2.8628 mL | 14.3139 mL | 28.6279 mL | |
| 5 mM | 0.5726 mL | 2.8628 mL | 5.7256 mL | |
| 10 mM | 0.2863 mL | 1.4314 mL | 2.8628 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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