Deconvolução de espectros UV diretamente de soluções de degradação forçada de fármacos

Abstract

Forced degradation studies (EDFs) are assays which pharmaceuticals are placed under stress conditions, which include acidic, basic, oxidative, high temperature, photodegradation, humidity and metal ions environments. The tests are performed to validate analytical methods that must be able to quantify active pharmaceutical ingredients (IFA) without interferences from any excipient or degradation product, and also detect the formed degradation products with acceptable resolution. EDFs can also be performed before finalizing the development of the product in order to obtain information on the intrinsic stability of the IFA and on the compatibility with excipients, which helps in the choice of these excipients, type of packaging and shelf life. For the validation of analytical methods, EDFs must promote an IFA degradation between 10% and 30%, according to regulatory agencies. Thus, companies must find the ideal degradation conditions for each product in each stress condition using chromatographic methods, which leads to an overspending of time and resources. Therefore, the present work aimed to directly identify the ideal degradation conditions by using UV-Vis spectroscopy, a simple, fast and low cost method. Allied to chemometric methodologies such as the multivariate resolution of curves (MCR), it was possible to estimate the conditions in which the active degrades within the expected range as well as the spectrum of the degradation products formed. The method was applied to four drugs: Acetylsalicylic Acid, Levocetirizine, Tamsulosin, Ticagrelor and proved to be very promising since it was possible to solve the pure spectral profiles of all the original components in addition to the relative concentration profiles.