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Pharm Res. 2010 Jul;27(7):1318-24. doi: 10.1007/s11095-010-0114-x. Epub 2010 Mar 31.
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.
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.
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.
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.
本研究的目的是分离和分析在含有聚乙二醇（PEG）的制剂中形成的西替利嗪降解产物，并阐明西替利嗪氧化的机制。
将含有 PEG 的基质中的西替利嗪置于 pH 值为 3 至 10 的强制降解条件下，并通过 HPLC 和 LC-MS/MS 对产物进行分析。此外，还通过过氧化氢和过碳酸钠对纯西替利嗪进行了选择性氧化。将反应混合物进行纯化，并通过（1）H NMR 对分离出的物质进行分析。
为了模拟含有 PEG 的制剂中西替利嗪的降解，对氧化过程进行了研究。基于西替利嗪的电离方案与强制降解结果的相关性，提出了氧化部位。通过将西替利嗪降解样品与西替利嗪 N-氧化物参比标准品混合进行验证。
聚乙二醇中西替利嗪的降解是由于药物与通过 PEG 氧化形成的过氧自由基等反应性过氧化物中间体之间的反应引起的。西替利嗪的选择性氧化和氧化产物的分离/表征，使得能够鉴定出氧化产物为西替利嗪 N-氧化物。提出了氧化机制。
