Isolation and characterization of cetirizine degradation product: mechanism of cetirizine oxidation.
OBJECTIVE
The goal of the study was to isolate and analyze a cetirizine degradation product, formed within a PEG-containing formulation and to elucidate the mechanism of oxidation of cetirizine.


METHODS
Cetirizine, formulated in PEG-containing matrix, was subjected to forced degradation conditions in the pH range from 3 to 10, and the product was analyzed by HPLC and LC-MS/MS. Additionally, pure cetirizine was subjected to selective oxidization by hydrogen peroxide and sodium percarbonate. The reaction mixture was purified, and the isolated material was analyzed by (1)H NMR.


RESULTS
Oxidation process was investigated in order to model the degradation of cetirizine in PEG-containing formulation. Site of oxidation is proposed based on correlation of the results of forced degradation with ionization scheme of cetirizine. The finding was verified by spiking of cetirizine degradation sample with cetirizine N-oxide reference standard.


CONCLUSIONS
Degradation of cetirizine in polyethylene glycol arose from the reaction between the drug and the reactive peroxide intermediates such as peroxyl radicals formed through oxidation of PEG. Selective oxidation of cetirizine and isolation/characterization of the oxidation product allowed the identification of the oxidation product as cetirizine N-oxide. The mechanism of oxidation is proposed.
Dyakonov
Tatyana
T
Banner Pharmacaps, 4125 Premier Drive, High Point, North Carolina 27265, USA. tadyakonov@banpharm.com
Muir
April
A
Nasri
Hassen
H
Toops
Dana
D
Fatmi
Aqeel
A
D017332:Cetirizine / Q000737:chemistry* / Q000302:isolation & purification; D002853:Chromatography, Liquid; D039563:Histamine H1 Antagonists, Non-Sedating / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000737:chemistry
D039563:Histamine H1 Antagonists, Non-Sedating; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D017332:Cetirizine