Vol.:(0123456789) 1 3 Chromatographia https://doi.org/10.1007/s10337-018-3526-0 REVIEW Chiral Method Development Strategies for HPLC using Macrocyclic Glycopeptide-Based Stationary Phases Priscila Aburachid Cardoso 1  · Isabela Costa César 1 Received: 6 February 2018 / Revised: 10 April 2018 / Accepted: 18 April 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Chiral HPLC methods using macrocyclic glycopeptide-based chiral stationary phases have been widely used and reported; however, the development of efcient methods to separate and quantify the analytes with high resolution is a challenging task. Therefore, the knowledge regarding the optimization of chromatographic parameters regarding this type of chiral chro- matography is essential. This review presents and discusses the optimization of HPLC conditions and parameters for the chiral resolution of racemic drugs on macrocyclic glycopeptide-based chiral stationary phases. Strategies for chiral method development are presented, using polar ionic, reversed phase, normal phase and polar organic modes. The efect of the most important chromatographic parameters, such as mobile phase composition, fow rate and temperature on the enantiosepara- tion are discussed aiming the adequate screening and optimization protocol for each mode. Keywords Chiral chromatography · Chirobiotic columns · Macrocyclic glycopeptide · Enantioseparation · Multimodal stationary phase Introduction It has long been known that enantiomers of drugs may have distinct pharmacodynamic (pharmacological and toxicologi- cal properties) and pharmacokinetic (absorption, distribu- tion, metabolism and excretion) activities, due to their dif- ferent biological interactions [1, 2]. Regarding chiral substances, it is generally postulated that there are four types of expected biological behaviour: desired biological activity is attributed to only one enanti- omer, while the other is inactive; enantiomers have identical pharmacological properties, both qualitatively and quantita- tively; the activity is qualitatively identical but quantitatively diferent between the stereoisomers; and the activities of the two enantiomers are qualitatively diferent [1, 3, 4]. The pharmacological activity of a drug depends primarily on its interaction with biological receptors, since the human body presents the ability to diferentiate enantiomeric pairs, due to the formation of diastereoisomeric complexes with diferent physicochemical properties and consequent difer- ent behaviours in the body. Therefore, it is understandable that enantiomers of a drug often exhibit diferent pharma- cological properties, thus they should be treated as diferent compounds. However, many chemical compounds, phar- maceutical drugs, fertilizers and food additives have been commercialized as racemic mixtures [5, 6]. Over the last quarter century, due to the growing under- standing and interest in stereoselective aspects and efects of chiral substances, a new concern has been raised about how to obtain pure enantiomers, increasing the demand to develop fast, simple and accurate analytical methods for enantiomer separation [3, 7]. Diferent analytical techniques are available for enan- tiomeric separation and identifcation, such as gas chroma- tography (GC), high performance liquid chromatography (HPLC), thin layer chromatography (TLC), supercritical fuid chromatography (SFC) and capillary electrophoresis (CE). The most widely used analytical method seems to be the direct separation of enantiomers using HPLC with com- mercially available chiral stationary phases (CSPs), owing to its simplicity and accuracy [2, 8, 9]. Since the late 1970s, considerable efort has been invested in the development of chiral stationary phases capable of * Isabela Costa César isacesar@gmail.com 1 Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil