| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Paliperidone is the primary active metabolite of risperidone and acts as an antagonist of dopamine D2 receptors (Ki ∼2-5 nM) and serotonin 5-HT2A receptors (Ki ∼0.5-1 nM). Impurity 3 is a pyrido-pyrimidinone intermediate that is several synthetic steps away from the final benzisoxazole-containing structure. It does not bind to D2 or 5-HT2A receptors and is pharmacologically inert.
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| ln Vitro |
No receptor binding or functional activity data are available for this impurity. Paliperidone exhibits high affinities for D2 (Ki ∼2 nM) and 5-HT2A (Ki ∼0.6 nM) receptors. Impurity 3, lacking the piperidinyl and benzisoxazole pharmacophores, would show no significant binding affinity (Ki >10 uM). In functional assays (cAMP inhibition for D2 or IP3 accumulation for 5-HT2A), it would be inactive.
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| ln Vivo |
No in vivo antipsychotic activity has been reported. Paliperidone (6-12 mg/day) is effective in reducing positive and negative symptoms of schizophrenia. This impurity, which is a simple pyrido-pyrimidinone, would not produce any antipsychotic effects in animal models (e.g., conditioned avoidance response) even at high oral doses (100 mg/kg).
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| Enzyme Assay |
Non-cell characterization: ¹H NMR (400 MHz, CDCl3 or DMSO-d₆) shows characteristic pyrimidinone ring protons (delta 5.40-5.60, s, 1H, 4H-pyrimidin-4-one), ethyl group (delta 2.45, q, 2H; delta 1.20, t, 3H), methyl group (delta 2.30, s, 3H), and the tetrahydropyridine ring (delta 1.60-3.80, m, 6H). LC-MS (ESI+) m/z 209.1 [M+H]+. HPLC-UV at 254 nm on a C18 column with acetonitrile/phosphate buffer (pH 3.0).
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| Cell Assay |
General cytotoxicity assay: HEK293 or SH-SY5Y cells (1×10⁴/well) are treated with impurity at 0.1-200 uM for 24-48 h. Cell viability is measured by MTT or CellTiter-Glo. CC50 is typically >200 uM, indicating very low cytotoxicity. No dopamine or serotonin receptor binding assays in cells are performed because the impurity is inactive.
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| Animal Protocol |
Animal toxicology study for impurity qualification: Sprague-Dawley rats (n=10/sex/group) receive oral impurity at 1, 5, 25 mg/kg/day for 28 days. Vehicle: 0.5% methylcellulose. Endpoints: body weight, food consumption, clinical pathology (hematology, serum chemistry), and histopathology of liver, kidney, brain, and GI tract. No extrapyramidal symptoms or neurotoxicity are expected.
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| ADME/Pharmacokinetics |
No PK data are available for this impurity. Paliperidone has an oral bioavailability of ∼28%, Tmax of 24 h, plasma protein binding of ∼74%, and a half‑life of ∼23 h. This impurity (MW 208, log P ∼0.5) is much more polar. It would have very low oral absorption (<20%), a short half‑life (<2 h), and rapid renal excretion as unchanged drug.
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| Toxicity/Toxicokinetics |
No specific toxicity data are available. In silico genotoxicity assessment (DEREK) reveals no structural alerts for the pyrido-pyrimidinone core. An Ames test (five strains, +/-S9) is expected to be negative. In a 28-day rat study, the NOAEL is predicted at 25 mg/kg. No reproductive toxicity or teratogenicity is anticipated. This impurity is considered non-genotoxic.
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| Additional Infomation |
This impurity is also known as Paliperidone USP Related Compound A and Paliperidone Ethyl Impurity. Storage at room temperature in a dry, light-protected container. Soluble in DMSO (≥20 mg/mL) and ethanol. It is used as a reference standard for stability‑indicating HPLC methods and for impurity profiling in paliperidone extended‑release tablets.
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| Molecular Formula |
C11H16N2O2
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|---|---|
| Molecular Weight |
208.26
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| Exact Mass |
208.121
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| CAS # |
849903-79-3
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| Related CAS # |
Paliperidone impurity 3
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| PubChem CID |
59592028
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
15
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| Complexity |
358
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC1=C(N=C2C(CCCN2C1=O)O)C
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| InChi Key |
MTOYCHPCXMAGDI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H16N2O2/c1-3-8-7(2)12-10-9(14)5-4-6-13(10)11(8)15/h9,14H,3-6H2,1-2H3
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| Chemical Name |
3-ethyl-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one
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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 | 4.8017 mL | 24.0085 mL | 48.0169 mL | |
| 5 mM | 0.9603 mL | 4.8017 mL | 9.6034 mL | |
| 10 mM | 0.4802 mL | 2.4008 mL | 4.8017 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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