Chemometrics Approaches in Forced Degradation Studies of Pharmaceutical Drugs

Abstract

Chemometrics is the chemistry field responsible for planning and extracting the maximum of information of experiments from chemical data using mathematical tools (linear algebra, statistics, and so on). Active pharmaceutical ingredients (APIs) can form impurities when exposed to excipients or environmental variables such as light, high temperatures, acidic or basic conditions, humidity, and oxidative environment. By considering that these impurities can affect the safety and efficacy of the drug product, it is necessary to know how these impurities are yielded and to establish the pathway of their formation. In this context, forced degradation studies of pharmaceutical drugs have been used for the characterization of physicochemical stability of APIs. These studies are also essential in the validation of analytical methodologies, in order to prove the selectivity of methods for the API and its impurities and to create strategies to avoid the formation of degradation products. This review aims to demonstrate how forced degradation studies have been actually performed and the applications of chemometric tools in related studies. Some papers are going to be discussed to exemplify the chemometric applications in forced degradation studies.

Importance of LCMS in Forced Degradation Studies for new Chemical Entities

“…The degradative pathways can be determined based on fragmentation patterns that are observed. After determination of degradant pathways, structure elucidations of degradants are done by synthesizing or isolating methods and further characterized by employing LC-MS, LC-UV, and LC-NMR techniques [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] .…”

Ispitivanje fizikalno-kemijske kompatibilnosti lijekova primjenom analitičkih tehnika: pregled istraživanja razvoja fiksne kombinacije 5-aminosalicilata i folne kiseline

“…U tablici 2 prikazani su okvirni uvjeti koji predstavljaju dobar početak za provedbu prisilne razgradnje. [85][86][87] Koncentracija stresora i vrijeme izlaganja ovise o stabilnosti ispitivanog spoja. Ako je spoj jako nestabilan u određenim uvjetima, potrebno je smanjiti koncentraciju stresora i obrnuto.…”

Multivariate Chemometric Comparison of Forced Degradation and Electrochemical Oxidation LC–MS Profiles of Maraviroc

“…Multivariate methods in analytical chemistry enable data reduction, grouping and classification of observations, as well as modeling of relationships that may exist between variables [ 8 ]. The application of chemometric tools such as Principal Component Analysis (PCA) or hierarchical cluster analysis (HCA) has proven to be efficient in obtaining better visualization of data even from low resolution and high noise levels of analytical measurements [ 9 ].…”