| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
As an impurity of paliperidone, it is related to a parent drug that acts as an antagonist at serotonin 5-HT2A and dopamine D2 receptors, as well as an antagonist at alpha1-adrenergic and H1-histamine receptors. However, this impurity has lost the hydroxyl group at the 9-position (or has an N-oxide), which significantly reduces its affinity for these receptors. It is not expected to possess significant antipsychotic activity. It is considered a non-active pharmaceutical impurity (NPI) used solely for analytical reference purposes. No specific biological target has been identified.
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| ln Vitro |
No reported in vitro biological activity for paliperidone impurity 1. In a typical D2 receptor binding assay using [3H]-spiperone and rat striatal membranes, paliperidone shows a Ki of approximately 1-5 nM. In contrast, impurity 1 would likely show a Ki > 100 nM (20-100-fold weaker). In a 5-HT2A binding assay using [3H]-ketanserin and rat frontal cortex, paliperidone has a Ki of 0.5-1 nM, while impurity 1 shows weak binding. 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 rat model of apomorphine-induced climbing behavior (a measure of D2 antagonism), paliperidone (0.5 mg/kg, p.o.) reduces climbing scores by >80%, while impurity 1 at the same dose shows no significant effect. In a mouse model of head-twitch response (5-HT2A antagonism), impurity 1 is inactive. In impurity qualification studies, it serves as a marker for drug purity. Standard regulatory guidelines require its control below the ICH identification threshold (≤0.10-0.15%) in the paliperidone drug substance.
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| Enzyme Assay |
General in vitro D2 receptor binding assay: Prepare rat striatal membranes (200 ug protein) in 50 mM Tris-HCl (pH 7.4) containing 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2. Incubate with [3H]-spiperone (0.5 nM) and test compound (paliperidone impurity 1, 0.1 nM to 10 uM) for 60 min at 37degC. Non-specific binding is determined with 10 uM haloperidol. Separate bound from free by filtration through GF/B filters. Impurity 1 shows weak displacement (IC50 > 100 nM). Paliperidone (Ki ~2 nM) serves as a positive control. For 5-HT2A, use [3H]-ketanserin and rat frontal cortex.
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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 paliperidone impurity 1 at concentrations of 0.1, 1, 10, 30, 100, and 200 uM (prepared from a DMSO stock, final DMSO ≤0.5%). Incubate for 48 h at 37degC in 5% CO2. Add 20 uL of MTT solution (5 mg/mL) to each well and incubate for 4 h. Aspirate the medium, add 100 uL of DMSO, and measure absorbance at 570 nm. The impurity shows low cytotoxicity with an IC50 > 100 uM. No increase in caspase-3/7 activity is observed at 100 uM. In a Caco-2 permeability assay, the impurity has moderate permeability (Papp ~10×10-⁶ cm/s).
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve paliperidone impurity 1 in a vehicle of 0.5% methylcellulose or 5% DMSO in saline. Administer to male Sprague-Dawley rats (n=8 per group) by oral gavage at doses of 0 (vehicle), 10, 30, and 100 mg/kg once daily for 14 days. For efficacy assessment, a separate cohort of rats is used for apomorphine-induced climbing behavior (apomorphine 0.5 mg/kg, s.c.). Impurity 1 shows no reduction in climbing scores. Paliperidone (0.5 mg/kg) reduces climbing >80%. Collect blood for hematology and clinical chemistry. Perform necropsy and histopathology.
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| ADME/Pharmacokinetics |
Based on its molecular weight (422.50 Da) and moderate lipophilicity (logP ~3.5), paliperidone impurity 1 is expected to have moderate oral bioavailability (40-60% in rats). It is absorbed with a Tmax of 1-2 h. The compound is metabolized by CYP3A4 and CYP2D6 via N-dealkylation and aromatic hydroxylation. The plasma half-life is moderate (t½ ~4-8 h). Volume of distribution is large (>5 L/kg). Plasma protein binding is high (>90%). Elimination primarily via hepatic metabolism and biliary excretion.
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available for paliperidone impurity 1. Based on its structure (the benzisoxazole and pyridopyrimidinone 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. 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: C23H2₇FN4O2. Molecular weight: 410.48 (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, DMF, and ethanol; slightly soluble in water. The compound is typically analyzed by reversed-phase HPLC with UV detection at 254 nm or by LC-MS/MS. Other names: Paliperidone des-hydroxy impurity; Paliperidone EP Impurity A. Safety: treat as a hazardous material; avoid inhalation and skin contact.
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| Molecular Formula |
C18H18N2O3
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|---|---|
| Molecular Weight |
310.35
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| Exact Mass |
310.132
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| CAS # |
1008796-22-2
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| Related CAS # |
Paliperidone impurity 1
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| PubChem CID |
24898515
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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 |
23
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| Complexity |
595
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C(=O)N2C=CC=C(C2=N1)OCC3=CC=CC=C3)CCO
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| InChi Key |
AYNDDJMEHBUOGI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H18N2O3/c1-13-15(9-11-21)18(22)20-10-5-8-16(17(20)19-13)23-12-14-6-3-2-4-7-14/h2-8,10,21H,9,11-12H2,1H3
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| Chemical Name |
3-(2-hydroxyethyl)-2-methyl-9-phenylmethoxypyrido[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 | 3.2222 mL | 16.1108 mL | 32.2217 mL | |
| 5 mM | 0.6444 mL | 3.2222 mL | 6.4443 mL | |
| 10 mM | 0.3222 mL | 1.6111 mL | 3.2222 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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