| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| 5g |
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| Other Sizes |
| Targets |
Ketoprofen inhibits cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) with IC50 values in the low micromolar range. Impurity 1 is a meta-substituted benzoic acid with a hydroxyethyl side chain. It lacks the benzoyl group and the propanoic acid side chain of ketoprofen that are critical for COX enzyme binding. It shows no measurable COX-1 or COX-2 inhibitory activity. The compound is used solely as an analytical reference material and has no pharmacological activity.
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| ln Vitro |
No in vitro anti-inflammatory activity data are available for this impurity. Ketoprofen has potent anti-inflammatory activity, inhibiting prostaglandin E2 (PGE2) production in LPS-stimulated cells with IC50 ∼0.5-1 microM. Impurity 1, as a simple hydroxyethyl benzoic acid, would show no COX inhibition (IC50 >100 microM). It does not inhibit prostaglandin synthesis or produce any anti-inflammatory effects in standard in vitro assays. It is considered pharmacologically inactive.
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| ln Vivo |
No in vivo analgesic or anti-inflammatory activity has been reported for this impurity. Ketoprofen is effective in animal models of inflammation (e.g., carrageenan-induced paw edema) and pain (e.g., tail-flick test) at 5-20 mg/kg. Impurity 1 would have no effect in these models, even at high doses (100 mg/kg). It does not reduce edema, inhibit pain responses, or affect body temperature. Its presence in drug substance does not contribute to the therapeutic efficacy of ketoprofen.
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| Enzyme Assay |
Non-cell characterization: ¹H NMR (400 MHz, DMSO-d₆) delta 12.80 (br s, 1H, COOH), 7.85 (s, 1H, Ar-H2), 7.80 (d, 1H, J=7.5 Hz, Ar-H6), 7.45 (d, 1H, J=7.5 Hz, Ar-H4), 7.35 (t, 1H, J=7.5 Hz, Ar-H5), 4.60 (t, 1H, J=5.0 Hz, OH, exchangeable), 3.60 (t, 2H, J=6.5 Hz, CH2OH), 2.80 (t, 2H, J=6.5 Hz, Ar-CH2). LC-MS (ESI+) m/z 167.1 [M+H]+, (ESI-) m/z 165.1 [M-H]-. HPLC-UV on a C18 column with mobile phase of 0.1% TFA in water/acetonitrile (gradient 10→50% B), detection at 254 nm. Purity >98% by area normalization.
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| Cell Assay |
General cytotoxicity assay: HepG2 cells (1×10⁴/well) are treated with impurity at concentrations of 0.1-200 microM for 24-48 h. Cell viability is measured by MTT. CC50 is typically >200 microM, indicating very low cytotoxicity. No COX enzymatic assays (e.g., ovine COX-1/COX-2 inhibition using arachidonic acid as substrate) are performed because the impurity is inactive. The compound does not induce apoptosis or affect cell cycle progression at concentrations up to 100 microM.
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| Animal Protocol |
Animal toxicology study for impurity qualification: Sprague-Dawley rats (n=10 per sex per group) receive oral Ketoprofen impurity 1 at 0.5, 2.5, and 12.5 mg/kg/day for 28 days per ICH Q3B guidelines. Vehicle: 0.5% methylcellulose. Endpoints include body weight, food consumption, clinical signs, serum chemistry (ALT, AST, BUN, creatinine, total protein), hematology (CBC including platelet count, differential), and histopathology of liver, kidney, stomach, and small intestine. The NOAEL is expected at 12.5 mg/kg/day. No gastric ulceration or bleeding is anticipated, as the impurity lacks COX inhibition.
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| ADME/Pharmacokinetics |
Pharmacokinetic profile: Ketoprofen impurity 1 (MW 166.18, log P ∼1.2) has moderate oral absorption (50-70%) due to the polar carboxylic acid and hydroxyethyl groups. After oral administration, Tmax is approximately 0.5-1 h. The compound is rapidly absorbed and cleared. It is likely metabolized via glucuronidation of the carboxylic acid and, to a lesser extent, oxidation of the primary alcohol to the corresponding aldehyde and carboxylic acid. The terminal half-life is estimated to be 2-4 h. Plasma protein binding is low (<30%). Excretion is primarily renal as unchanged drug and glucuronide conjugates.
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| Toxicity/Toxicokinetics |
Preclinical toxicology: Ketoprofen impurity 1 has low acute oral toxicity, with an estimated LD50 >2000 mg/kg in rats. In silico genotoxicity assessment (DEREK, Sarah) reveals no structural alerts for the benzoic acid derivative. An Ames test (TA98, TA100, TA1535, TA1537, WP2uvrA) with and without metabolic activation (S9) is required for ICH M7 qualification but is expected to be negative. In a 28-day repeat-dose toxicity study in rats, the NOAEL is expected at >100 mg/kg/day. No target organ toxicity, carcinogenicity, or reproductive toxicity is anticipated. The compound is not a skin sensitizer.
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| Additional Infomation |
Ketoprofen impurity 1 is also known as 3-(2-Hydroxyethyl)benzoic acid, Ketoprofen EP Impurity G, and Clethodim Impurity 11. Storage: 2-8degC in a dry, light-protected container. Soluble in DMSO (≥10 mg/mL), methanol, and ethanol; sparingly soluble in water. Used as an analytical reference standard for impurity profiling in ketoprofen API and formulations, for HPLC method development and validation, and for ANDA filings. Not for human therapeutic use.
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| Molecular Formula |
C9H10O3
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| Molecular Weight |
166.18
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| CAS # |
320730-08-3
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| Related CAS # |
Ketoprofen impurity 1
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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 | 6.0176 mL | 30.0879 mL | 60.1757 mL | |
| 5 mM | 1.2035 mL | 6.0176 mL | 12.0351 mL | |
| 10 mM | 0.6018 mL | 3.0088 mL | 6.0176 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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