product Description
Netupitant(chemical name: 2-[3,5-bis(trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-
(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide; CAS No.: 290297-26-6; molecular formula: C₃₀H₃₂F₆N₄O; molecular weight: 578.59) is a selective neurokinin 1 (NK1) receptor antagonist with long-acting antiemetic activity. It blocks CNS NK1 receptors to inhibit substance P binding, effectively preventing chemotherapy-induced delayed nausea and vomiting. Striatal NK1 receptor occupancy reaches 90% at 2.2 hours post-administration and remains above 75% after 120 hours.
As a core bulk drug for formulation production, netupitant is a white to off-white solid with a melting point of 156.2–160.0°C, density of ~1.255–1.3g/cm³, slight solubility in chloroform/DMSO/methanol, and a pKa of ~7.89. It should be stored sealed at 2–8°C to maintain stability.
For quality control, netupitant complies with strict bulk drug standards: purity ≥98% (HPLC); related substances (individual ≤0.1%, total ≤2.0%), focusing on intermediates and degradants; appearance (white to off-white solid, no obvious impurities) and identification (infrared spectroscopy + HPLC retention time). It also controls content uniformity, dissolution, residual solvents (methanol ≤0.3%, ethanol ≤0.5%), heavy metals (≤10 ppm), loss on drying (≤0.5%) and residue on ignition (≤0.1%) to ensure batch consistency. Clinically, it combines with palonosetron in Akynzeo® (300mg + 0.5mg) for acute/delayed CINV from high/moderate emetogenic chemotherapy, with a recommended oral dose 1 hour pre-chemotherapy (with/without food), no adjustment for mild-moderate renal impairment, age, gender or race.
Well-tolerated, it has mild-to-moderate adverse reactions (headache, fatigue, dyspepsia, constipation). It is not recommended for pregnant/lactating women (unless benefit outweighs risk) or severe hepatic/renal impairment; caution for moderate hepatic impairment, no adjustment for mild cases.
product Specification
|
Item |
Unit |
Specification |
|
Appearance |
|
white to off-white ,solid |
|
Solubility |
|
slight solubility in chloroform/DMSO/methanol |
|
Melting point |
℃ |
156.2–160.0 |
|
Identification |
|
infrared spectroscopy + HPLC retention time |
|
Dechlorinated impurity |
% |
≤0.1 |
|
Other impurities |
% |
≤0.1 |
|
Related Substances - Total Impurities |
% |
≤2.0 |
|
Main peak purity |
% |
≥98.00 |
|
Residual solvents |
% |
methanol ≤0.3, ethanol ≤0.5 |
|
Loss on drying |
% |
≤0.5 |
|
Residue on ignition |
% |
≤0.1 |
|
Heavy metals |
ppm |
≤10 |
|
Storage |
|
sealed, dry container at 2–8℃ |
description2