Multiblock modelling on the study of the kinetic degradation of rosuvastatin calcium in the presence of retention time shifts and rank deficiency

• Published in: Analytica chimica acta 2020-10, Vol.1133, p.77-87
• Main Authors: Pinto, Licarion, Jardim, Isabel Cristina Sales Fontes, Rutledge, Douglas Neil, Breitkreitz, Márcia Cristina
• Format: Article
• Language: English
• Subjects: Analytical chemistry; Calcium rosuvastatin; Chemical Sciences; Chromatography, High Pressure Liquid; Chromatography, Liquid; Drug Stability; Forced degradation study; Kinetics; Liquid chromatography; Models, Chemical; Multivariate curve resolution; Multiway; Non-quadrilinear; Rosuvastatin Calcium
• ISSN: 0003-2670; 1873-4324
• DOI: 10.1016/j.aca.2020.08.008

In pharmaceutical development, forced degradation studies are mandatory before the commercialization of any drug product. They aim at identifying the possible degradation routes and the potential products that may be formed during drug product shelf life. The most widely used techniques for monitoring this in the pharmaceutical industry are hyphenated techniques such as Liquid Chromatography coupled to ultraviolet diode array detector (LC-DAD). There are however some drawbacks, such as long analysis times required for the elution of all compounds and coelution, which is not easily detected since degradation products usually have spectra very similar to that of the drug. Chemometrics methods applied to LC-DAD data are capable of solving this issue, but the approaches described in the literature first require peak alignment to solve the rank deficiency problem, which is a delicate preprocessing method for high order data. The present work describes another approach where extra information - the kinetic degradation profiles - is included for the modelling, generating a third-order data set for each sample, resulting in a four-way array (sample x retention times x spectra x degradation profile). This approach has the advantage of using the information in the third mode to solve the peak co-elution problem without the need for peak alignment among samples. With the proposed approach, it was possible to study the degradation of calcium rosuvastatin, a modern cholesterol lowering drug, using a 2 min-run, despite all the challenges in the modelling of this data. The proposed strategy was compared to an approach based on augmenting the matrix in the spectral/kinetic modes (second order modelling strategy). [Display omitted] •Rosuvastatin acidic degradation products detected in a very short chromatographic run.•Rosuvastatin degradation study assisted by chemometrics approaches.•Multiway strategies for analysis of coeluted constituents with identical and correlated spectra in forced degradation study.•Third order advantage to overcome quadrilinearity breakdowns and rank deficiency.