Nucleus of Physical and Chemical Testing in Medicines (NFQM), School of Pharmaceutical Sciences, University of São Paulo (USP), Sao Paulo, Brazil.
Adolfo Lutz Institute (IAL); Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), Sao Paulo, Brazil.
Pharmazie. 2021 Apr 1;76(4):138-144. doi: 10.1691/ph.2021.0126.
Ibuprofen soft gelatin capsules were subjected to degradation under acidic, basic, oxidation, photolytic, thermal, humidity, and metal ions conditions. To analyse the degradation products, a reversed-phase liquid chromatography (RP-LC) indicative stability method was successfully developed. Chromatographic separation was achieved using a Poroshell HPH-C18 150 x 4.6 mm, 4 μm, column at 25 °C, with a mobile phase constituted by 0.1% phosphoric acid and acetonitrile in gradient at a flow rate of 1.0 mL• min , using ultraviolet detection at 220 nm and injection volume of 20 μL. In total, eight unknown impurities were found. The peaks RRt 0.49, RRt 0.75, and RRt 0.95 were above 0.17%, corresponding to the identification threshold. Those were identified and characterized by LC-MS-QTOF, with the same chromatographic conditions, except for the exchange of 0.1% phosphoric acid for 0.1% formic acid. The impurities originated from the interaction of ibuprofen with excipients: esterification with PEG, with sorbitol/sorbitan, and with glycerol by-products, which has not yet been reported in the literature. The developed method can be used in several pharmaceutical areas as quality control of impurities, studies of forced degradation, and for the development of future formulations.
布洛芬软胶囊在酸性、碱性、氧化、光解、热、湿度和金属离子条件下进行降解。为了分析降解产物，成功开发了一种反相液相色谱（RP-LC）指示稳定性方法。在 25°C 下，使用 Poroshell HPH-C18 150 x 4.6mm，4μm 柱，以 0.1%磷酸和乙腈的梯度组成流动相，流速为 1.0mL·min-1，在 220nm 处进行紫外检测，进样量为 20μL，实现了色谱分离。总共发现了 8 种未知杂质。RRt 0.49、RRt 0.75 和 RRt 0.95 的峰高于 0.17%，对应于鉴定阈值。这些杂质通过 LC-MS-QTOF 进行了鉴定和表征，除了交换 0.1%磷酸为 0.1%甲酸外，其余色谱条件相同。杂质来源于布洛芬与赋形剂的相互作用：与 PEG、山梨糖醇/山梨聚糖和甘油副产物的酯化，这在文献中尚未报道过。所开发的方法可用于药物制剂的多个领域，如杂质的质量控制、强制降解研究以及未来制剂的开发。
