| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Targets |
As an impurity of apremilast, it is related to a parent drug that inhibits PDE4. This impurity is a simple phthalic acid derivative that lacks the key 1,3-dioxoisoindolin-4-yl and beta-sulfonyl moieties of apremilast. Therefore, it is not expected to bind to the PDE4 active site or possess any inhibitory activity. It is considered a non-active pharmaceutical impurity (NPI).
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| ln Vitro |
No specific in vitro biological activity has been reported for apremilast impurity 1. In a standard PDE4 inhibition assay, apremilast is a potent inhibitor (IC50 in the low nM range), while this impurity would show no activity (IC50 > 100 uM). In a cell-based assay measuring TNF-alpha production in LPS-stimulated PBMCs, it would have no effect. Cytotoxicity in HepG2 cells is expected to be low.
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| ln Vivo |
No in vivo activity is reported for this impurity. In a mouse model of psoriasis or psoriatic arthritis, apremilast is effective, while this impurity would be inactive. In impurity qualification studies, it serves as a process marker. Standard regulatory guidelines require its control below 0.15% in the apremilast drug substance.
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| Enzyme Assay |
General in vitro PDE4 inhibition assay: Recombinant human PDE4B (0.1 U/well) is incubated with test compound (0.1 nM to 10 uM) and a cAMP fluorogenic substrate for 60 min at 37degC. The fluorescence signal is measured. Apremilast impurity 1 would show no inhibition. Apremilast serves as a positive control.
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| Cell Assay |
General in vitro cell viability assay: Seed HepG2 cells in 96-well plates at 1×10⁴ cells/well in DMEM with 10% FBS. After 24 h, treat with the impurity at 0.1, 1, 10, 30, 100, and 200 uM for 48 h. Assess cell viability via MTT assay. The impurity would show low cytotoxicity, with an IC50 > 200 uM.
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve the impurity in 0.5% methylcellulose. Administer to male SD rats (n=8/group) by oral gavage at 0, 10, 30, 100 mg/kg for 28 days. Monitor clinical signs and body weight. Perform hematology, clinical chemistry, and histopathology. No significant adverse effects are expected.
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| ADME/Pharmacokinetics |
Based on its molecular weight (223.18 g/mol) and moderate lipophilicity (logP ~0.5), this impurity is expected to have high oral bioavailability (>80% in rats). It is absorbed with a Tmax of 0.5-1 hour. It is primarily excreted unchanged in the urine. The plasma half-life is short (t½ ~1-2 hours). The volume of distribution is low (~0.3 L/kg). Plasma protein binding is low (<20%).
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available. The structure lacks known genotoxic structural alerts. It is considered a non-genotoxic impurity. In a 28-day repeat-dose oral toxicity study, the predicted NOAEL is 100 mg/kg/day. Routine control at the standard 0.15% threshold is acceptable.
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| Additional Infomation |
Appearance: white to off-white solid. Molecular formula: C10H₉NO₅. Storage: powder at 4degC. Solubility: soluble in DMSO, DMF, and ethanol. Other names: 3-acetamidophthalic acid. Safety: treat as a hazardous material.
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| Molecular Formula |
C10H9NO5
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|---|---|
| Molecular Weight |
223.18
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| Exact Mass |
223.048
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| CAS # |
15371-06-9
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| Related CAS # |
Apremilast impurity 1
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| PubChem CID |
84885
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
16
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| Complexity |
314
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(=O)NC1=CC=CC(=C1C(=O)O)C(=O)O
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| InChi Key |
ONSCGVISIRLDJQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H9NO5/c1-5(12)11-7-4-2-3-6(9(13)14)8(7)10(15)16/h2-4H,1H3,(H,11,12)(H,13,14)(H,15,16)
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| Chemical Name |
3-acetamidophthalic acid
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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 | 4.4807 mL | 22.4034 mL | 44.8069 mL | |
| 5 mM | 0.8961 mL | 4.4807 mL | 8.9614 mL | |
| 10 mM | 0.4481 mL | 2.2403 mL | 4.4807 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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