Comprehensive Assessment of Degradation Behavior of Simvastatin by UHPLC/MS Method, Employing Experimental Design Methodology.

Maja Hadzieva Gigovska,Natalija Nakov,Aneta Dimitrovska,Sonja Ugarkovic,Packa Antovska,Ana Petkovska,Jelena Acevska

doi:10.1155/2018/7170539

Abstract

This manuscript describes comprehensive approach for assessment of degradation behavior of simvastatin employing experimental design methodology as scientific multifactorial strategy. Experimental design methodology was used for sample preparation and UHPLC method development and optimization. Simvastatin was subjected to stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. Using 2n full factorial design degradation conditions were optimized to obtain targeted level of degradation. Screening for optimal chromatographic condition was made by Plackett–Burman design and optimization chromatographic experiments were conducted according to Box-Behnken design. Successful separation of simvastatin from the impurities and degradation products was achieved on Poroshell 120 EC C18 50 × 3.0 mm 2.7 μm, using solutions of 20 mM ammonium formate pH 4.0 and acetonitrile as the mobile phase in gradient mode. The proposed method was validated according to International Conference on Harmonization (ICH) guidelines. Validation results have shown that the proposed method is selective, linear, sensitive, accurate, and robust and it is suitable for quantitative determination of simvastatin and its impurities. Afterwards, the degradation products were confirmed by a direct hyphenation of liquid chromatograph to ion-trap mass spectrometer with heated electrospray ionization interface. This study highlights the multiple benefits of implementing experimental design, which provides a better understanding of significant factors responsible for degradation and ensures successful way to achieve degradation and can replace the trial and error approach used in conventional forced degradation studies.

Highlights

To meet the demands of modern pharmaceutical analysis, the employment of chemometrical tools in every possible way during analysis is necessary, since many variables can be simultaneously controlled to achieve the desired results through limited experimental trials
This study highlights the multiple benefits of implementing experimental design, which provides a better understanding of significant factors responsible for degradation and ensures successful way to achieve degradation and can replace the trial and error approach used in conventional forced degradation studies
Use of such systematic approach would be a necessity for any extensive study, such as forced degradation studies (FDS) for stability assessment of the active pharmaceutical ingredients (APIs) and finished dosage forms (FDFs)

Summary

Introduction

To meet the demands of modern pharmaceutical analysis, the employment of chemometrical tools in every possible way during analysis is necessary, since many variables can be simultaneously controlled to achieve the desired results through limited experimental trials. The use of an experimental design (DoE) approach by which multivariate data can be handled and fitted to an empirical function is justifiable because it offers a better choice over one factor at time (OFAT) for identification and control of critical factors [1, 2]. In this direction, use of such systematic approach would be a necessity for any extensive study, such as forced degradation studies (FDS) for stability assessment of the active pharmaceutical ingredients (APIs) and finished dosage forms (FDFs). Far from our knowledge, none of the reported analytical procedures describe simple and satisfactory sample preparation methodology where the influences of the stressor strength, time of expose, and temperature are evaluated

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