Analytical quality by design-based development of a capillary electrophoresis method for Omeprazole impurity profiling.

Omeprazole (OME) is a proton pump inhibitor used to treat gastroesophageal reflux disease associated conditions. The current study presents an Analytical Quality by Design-based approach for the development of a CE method for OME impurity profiling. The scouting experiments suggested the selection of solvent modified Micellar ElectroKinetic Chromatography operative mode using a pseudostationary phase composed of sodium dodecyl sulfate (SDS) micelles and n-butanol as organic modifier in borate buffer. A symmetric three-level screening matrix 37//16 was used to evaluate the effect of Critical Method Parameters, including Background Electrolyte composition and instrumental settings, on Critical Method Attributes (critical resolution values, OME peak width and analysis time). The analytical procedure was optimized using Response Surface Methodology through a Central Composite Orthogonal Design. Risk of failure maps made it possible to define the Method Operable Design Region, within which the following optimized conditions were selected: 72 mM borate buffer pH 10.0, 96 mM SDS, 1.45 %v/v n-butanol, capillary temperature 21 °C, applied voltage 25 kV. The method was validated according to ICH guidelines and robustness was evaluated using a Plackett-Burman design. The developed procedure enables the simultaneous determination of OME and seven related impurities, and has been successfully applied to the analysis of pharmaceutical formulations.

Phytocannabinoids: Exploring Pharmacological Profiles and Their Impact on Therapeutical Use.

Phytocannabinoids, a diverse group of naturally occurring compounds extracted from the Cannabis plant, have attracted interest due to their potential pharmacological effects and medicinal uses. This comprehensive review presents the intricate pharmacological profiles of phytocannabinoids while exploring the diverse impacts these substances have on biological systems. From the more than one hundred cannabinoids which were identified in the Cannabis plant so far, cannabidiol (CBD) and tetrahydrocannabinol (THC) are two of the most extensively studied phytocannabinoids. CBD is a non-psychoactive compound, which exhibits potential anti-inflammatory, neuroprotective, and anxiolytic properties, making it a promising candidate for a wide array of medical conditions. THC, known for its psychoactive effects, possesses analgesic and antiemetic properties, contributing to its therapeutic potential. In addition to THC and CBD, a wide range of additional phytocannabinoids have shown intriguing pharmacological effects, including cannabichromene (CBC), cannabigerol (CBG), and cannabinol (CBN). The endocannabinoid system, made up of the enzymes involved in the production and breakdown of endocannabinoids, cannabinoid receptors (CB1 and CB2), and endogenous ligands (endocannabinoids), is essential for preserving homeostasis in several physiological processes. Beyond their effects on the endocannabinoid system, phytocannabinoids are studied for their ability to modify ion channels, neurotransmitter receptors, and anti-oxidative pathways. The complex interaction between phytocannabinoids and biological systems offers hope for novel treatment approaches and lays the groundwork for further developments in the field of cannabinoid-based medicine. This review summarizes the state of the field, points out information gaps, and emphasizes the need for more studies to fully realize the therapeutic potential of phytocannabinoids.

Comprehensive Review on Chiral Stationary Phases in Single-Column Simultaneous Chiral-Achiral HPLC Separation Methods.

This comprehensive review explores the utilization of chiral stationary phases (CSPs) in the context of single-column simultaneous chiral-achiral high-performance liquid chromatography (HPLC) separation methods. While CSPs have traditionally been pivotal for enantioselective drug analysis, contemporary CSPs often exhibit notable chemoselective properties. Consequently, there is a discernible trend towards the development of methodologies that enable simultaneous enantio- and chemoselective separations utilizing a single CSP-based chromatographic column. This review provides an exhaustive overview of reported HPLC methods in this domain, with a focus on four major CSP types: cyclodextrin-, glycopeptide antibiotic-, protein-, and polysaccharide-based CSPs. This article delves into the diverse applications of CSPs, encompassing various chromatographic modes such as normal phase (NP), reverse phase (RP), and polar organic (PO). This review critically discusses method development, emphasizing the additional chemoselective separation mechanisms of CSPs. It also explores possibilities for method optimization and development, concluding with future perspectives on this evolving field. Despite the inherent challenges in understanding the retention mechanisms involved in chemoselective separations, this review highlights promising trends and anticipates a growing number of simultaneous enantio- and chemoselective methods in pharmaceutical analyses, pharmacokinetic studies, and environmental sample determinations.

Quality by design-guided development of a capillary electrophoresis method for the simultaneous chiral purity determination and impurity profiling of tamsulosin.

Analytical Quality by Design principles using the design of experiments were applied for the development of a capillary electrophoresis method for the determination of enantiomeric purity and chemically related impurities of tamsulosin. From initial scouting experiments, a dual cyclodextrin (CD) system composed of sulfated ß-CD and carboxymethyl-α-CD was selected as the chiral selector. A fractional factorial resolution V+ design was used for the identification of the critical process parameters, while a face-centered central composite design and Monte Carlo simulations were employed for final optimization and defining the design space of the method. The experimental conditions of the working point were: 30 mM sodium phosphate buffer, pH 3.0, containing 40 mg/mL sulfated ß-CD and 7 mg/mL carboxymethyl-α-CD, capillary temperature 18°C, applied voltage -23 kV. Following the assessment of robustness by applying a Plackett-Burman design, the method was validated according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use guideline Q2(R1). The method allowed the quantification of the chiral impurity and three other related impurities at the 0.1 % level with acceptable accuracy and precision.

The Role of Five-Membered Heterocycles in the Molecular Structure of Antibacterial Drugs Used in Therapy.

Five-membered heterocycles are essential structural components in various antibacterial drugs; the physicochemical properties of a five-membered heterocycle can play a crucial role in determining the biological activity of an antibacterial drug. These properties can affect the drug's activity spectrum, potency, and pharmacokinetic and toxicological properties. Using scientific databases, we identified and discussed the antibacterials used in therapy, containing five-membered heterocycles in their molecular structure. The identified five-membered heterocycles used in antibacterial design contain one to four heteroatoms (nitrogen, oxygen, and sulfur). Antibacterials containing five-membered heterocycles were discussed, highlighting the biological properties imprinted by the targeted heterocycle. In some antibacterials, heterocycles with five atoms are pharmacophores responsible for their specific antibacterial activity. As pharmacophores, these heterocycles help design new medicinal molecules, improving their potency and selectivity and comprehending the structure-activity relationship of antibiotics. Unfortunately, particular heterocycles can also affect the drug's potential toxicity. The review extensively presents the most successful five-atom heterocycles used to design antibacterial essential medicines. Understanding and optimizing the intrinsic characteristics of a five-membered heterocycle can help the development of antibacterial drugs with improved activity, pharmacokinetic profile, and safety.

A Comprehensive Bibliographic Review Concerning the Efficacy of Organic Acids for Chemical Peels Treating Acne Vulgaris.

Acne vulgaris stands out as the most prevalent skin disorder among teenagers and young adults, causing physical discomfort and considerable economic and psychological burdens on individuals and society. A wide range of topical and systemic therapies are available in acne treatment. Chemical peeling is a skin resurfacing technique designed to rebuild healthy skin using exfoliating substances, a simple and affordable process with various dermatological uses. Chemical peels, classified as superficial, medium, and deep, have been utilized for acne vulgaris and multiple other skin issues. In these chemical peels, a diverse range of chemical substances is employed, each with its unique mode of action. Among these, α-hydroxy and ß-hydroxy acids have gathered attention for their efficacy in reducing acne lesions and enhancing overall skin appearance. Acids, such as salicylic acid, glycolic acid, or lactic acid, are commonly used in chemical peels due to their exfoliating and sebum-regulating properties. Despite the widespread use of these acids, there exists a lack of consensus regarding the most effective acid type and concentration for treating acne-prone skin. This review aims to bridge this knowledge gap by evaluating the effectiveness and safety of various organic acids used in chemical peels specifically for acne-prone skin. The findings of this comprehensive bibliographic review indicate that organic acid-based chemical peels represent effective and safe treatment options for individuals with acne-prone skin. Their adaptability sets these treatments apart; the choice of organic acid can be tailored to meet individual patient needs and tolerability levels. This personalized approach ensures that patients receive optimal care while minimizing the risks associated with the treatment. As research in this field progresses, it is anticipated that a more nuanced understanding of the ideal acid type and concentration will emerge, further enhancing the efficacy and safety of chemical peels for acne-prone skin.

Simultaneous determination of enantiomeric and organic impurities of vildagliptin on a cellulose tris(3-chloro-4-methylphenylcarbamate) column under revered-phase conditions.

A new, reversed-phase HPLC (RP-HPLC) method was developed for the simultaneous determination of the dipeptidyl-peptidase-IV-inhibitor antidiabetic drug vildagliptin (VIL) enantiomeric impurity and four other achiral related impurities. An initial screening was performed on five polysaccharide-type chiral stationary phases (Lux Amylose-1, Lux Amylose-2, Lux-Cellulose-1, Lux-Cellulose-2, Lux-Cellulose-3) in polar organic mode with methanol, ethanol, 2-propanol, or acetonitrile containing 0,1% diethylamine as mobile phase to identify the best conditions for the separation of VIL enantiomers. Lux-Cellulose-2 column was found to provide the best chiral resolution for VIL enantiomers. Further experiments were conducted using different aqueous-organic mobile phases to achieve the simultaneous chiral-achiral separation of the selected compounds. Experimental design-based optimization was performed by using a face-centered central composite design. The optimal separation conditions (Lux Cellulose-2 stationary phase, 45 °C, mobile phase consisting of methanol/water/diethylamine 80:20:0.2 (v/v/v), and 0.45 mL/min flow rate) provided baseline separation for all 6 compounds. The optimized method was validated according to the ICH guideline and proved to be reliable, specific, linear, precise, and accurate for the determination of at least 0.1% for all impurities in VIL samples. The validated method was applied for determinations from a commercially available drug formulation and proved to be suitable for routine quality control of both enantiomeric and organic impurities of VIL.

Applications of Capillary Electrophoresis for the Determination of Cannabinoids in Different Matrices.

Cannabinoids, terpenophenolic chemicals found only in cannabis, are primarily responsible for cannabis pharmacologic effects; nearly 150 distinct cannabinoids have been identified thus far. Among these, the main psychoactive molecule, tetrahydrocannabinol (THC), and the non-psychoactive counterpart, cannabidiol (CBD) are distinguishable. In the past decade, a CBD-containing pharmaceutical preparation was approved by Food and Drug Administration (FDA) for the treatment of drug-resistant epileptic seizures in children, and research trials for a variety of additional medical conditions for which CBD has been suggested as a therapy are being conducted. Additionally, the number of "CBD-containing" dietary supplements, largely available online, is increasing rapidly. Consequently, the necessity for the development of qualitative and quantitative methodologies for the analysis of the bioactive components of Cannabis is rising because of the increase in the production of therapeutic cannabis products. One of the analytical methods with good potential in cannabinoids analysis is capillary electrophoresis (CE). It has advantages related to high separation efficiency, relatively short analysis time, and the small consumption of analytes and reagents which generates relatively lower operational costs than other methods. This review focuses on the use of CE techniques to examine biological matrices and plant materials for the presence of cannabinoids and other bioactive compounds found in cannabis. The advantages, drawbacks, and applicability of the various electromigration approaches are also assessed. The article provides an overview of the "state of the art" and the latest trends in CE-based methods for the determination of cannabinoids.

Quality by design-guided development of a capillary electrophoresis method for the chiral purity determination of silodosin.

Silodosin is a single isomer selective α1-adrenoreceptor antagonist used for the treatment of benign prostatic hyperplasia. In order to control the enantiomeric purity of the drug a capillary electrophoresis method was developed that is applicable to the analysis of drug substance as well as pharmaceutical formulations. Method development followed a quality by design strategy. After selection of carboxymethyl-ß-cyclodextrin as suitable chiral selector and the starting conditions in the scouting phase, a two-level full factorial design was applied to identify the critical process parameters. The final method optimization was performed using a face-centered central composite design resulting in the conditions 100 mM sodium phosphate buffer, pH 2.9, containing 40 mg/mL car-boxymethyl-ß-cyclodextrin, a capillary temperature of 17 °C and an applied voltage of 28 kV. Robustness testing employing a Plackett-Burman design revealed the importance of careful pH adjustment in order to achieve suitable peak shape and resolution. The method was validated according to the guideline Q2(R1) of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use and applied to the analysis of a commercial capsule formulation.

New Trends in the Quality Control of Enantiomeric Drugs: Quality by Design-Compliant Development of Chiral Capillary Electrophoresis Methods.

Capillary electrophoresis (CE) is a potent method for analyzing chiral substances and is commonly used in the enantioseparation and chiral purity control of pharmaceuticals from different matrices. The adoption of Quality by Design (QbD) concepts in analytical method development, optimization and validation is a widespread trend observed in various analytical approaches including chiral CE. The application of Analytical QbD (AQbD) leads to the development of analytical methods based on sound science combined with risk management, and to a well understood process clarifying the influence of method parameters on the analytical output. The Design of Experiments (DoE) method employing chemometric tools is an essential part of QbD-based method development, allowing for the simultaneous evaluation of experimental parameters as well as their interaction. In 2022 the International Council for Harmonization (ICH) released two draft guidelines (ICH Q14 and ICH Q2(R2)) that are intended to encourage more robust analytical procedures. The ICH Q14 guideline intends to harmonize the scientific approaches for analytical procedures' development, while the Q2(R2) document covers the validation principles for the use of analytical procedures including the recent applications that require multivariate statistical analyses. The aim of this review is to provide an overview of the new prospects for chiral CE method development applied for the enantiomeric purity control of pharmaceuticals using AQbD principles. The review also provides an overview of recent research (2012-2022) on the applicability of CE methods in chiral drug impurity profiling.

Chiral Discrimination of Mexiletine Enantiomers by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors and Experimental Design Method Optimization.

Mexiletine (MXL) is a class IB antiarrhythmic agent, acting as a non-selective voltage-gated sodium channel blocker, used in therapy as a racemic mixture R,S-MXL hydrochloride. The aim of the current study was the development of a new, fast, and efficient method for the chiral separation of MXL enantiomers using capillary electrophoresis (CE) and cyclodextrins (CDs) as chiral selectors (CSs). After an initial CS screening, using several neutral and charged CDs, at four pH levels, heptakis-2,3,6-tri-O-methyl-ß-CD (TM-ß-CD), a neutral derivatized CD, was chosen as the optimum CS for the enantioseparation. For method optimization, an initial screening fractional factorial design was applied to identify the most significant parameters, followed by a face-centered central composite design to establish the optimal separation conditions. The best results were obtained by applying the following optimized electrophoretic conditions: 60 mM phosphate buffer, pH 5.0, 50 mM TM-ß-CD, temperature 20 °C, applied voltage 30 kV, hydrodynamic injection 50 mbar/s. MXL enantiomers were baseline separated with a resolution of 1.52 during a migration time of under 5 min; S-MXL was the first migrating enantiomer. The method's analytical performance was verified in terms of precision, linearity, accuracy, and robustness (applying a Plackett-Burman design). The developed method was applied for the determination of MXL enantiomers in pharmaceuticals. A computer modeling of the MXL-CD complexes was applied to characterize host-guest chiral recognition.

Development and Evaluation of Cannabidiol Orodispersible Tablets Using a 23-Factorial Design.

Orodispersible tablets (ODTs) are pharmaceutical formulations used to obtain fast therapeutic effects, usually recommended for geriatric and pediatric patients due to their improved compliance, bioavailability, ease of administration, and good palatability. This study aimed to develop ODTs with cannabidiol (CBD) phytocannabinoid extracted from Cannabis sativa used in the treatment of Lennox-Gastaut and Dravet syndromes. The tablets were obtained using an eccentric tableting machine and 9 mm punches. To develop CBD ODTs, the following parameters were varied: the Poloxamer 407 concentration (0 and 10%), the type of co-processed excipient (Prosolv® ODT G2-PODTG2 and Prosolv® EasyTab sp-PETsp), and the type of superdisintegrant (Croscarmellose-CCS, and Soy Polysaccharides-Emcosoy®-EMCS), resulting in eleven formulations (O1-O11). The following dependent parameters were evaluated: friability, disintegration time, crushing strength, and the CBD dissolution at 1, 3, 5, 10, 15, and 30 min. The dependent parameters were verified according to European Pharmacopoeia (Ph. Eur.) requirements. All the tablets obtained were in accordance with quality requirements in terms of friability (less than 1%), and disintegration time (less than 180 s). The crushing strength was between 19 N and 80 N. Regarding the dissolution test, only four formulations exhibited an amount of CBD released higher than 80% at 30 min. Taking into consideration the results obtained and using the Modde 13.1 software, an optimal formulation was developed (O12), which respected the quality criteria chosen (friability 0.23%, crushing strength of 37 N, a disintegration time of 27 s, and the target amount of CBD released in 30 min of 99.3 ± 6%).

The Use of Antibiotics as Chiral Selectors in Capillary Electrophoresis: A Review.

Chirality is becoming an essential issue in modern pharmaceutical research as regulatory agencies emphasize the safety and efficiency of enantiomers in drug development. The development of efficient and reliable chiral separation methods became a necessity in the last 30 years, and capillary electrophoresis (CE), due to its relatively low costs and "green" features, is attracting increased attention. Cyclodextrin (CD) and their derivatives are the most frequently used chiral selectors (CSs) in CE, however, the use of antibiotics as CSs represents an interesting alternative. Various classes of antibiotics (aminoglycosides, ansamycins, glycopeptides, lincosamides, macrolides, tetracyclines) have been used more or less successfully for the enantio-separation of pharmaceuticals. Antibiotics offer the possibility of a multitude of potential interactions (electrostatic, inclusion, hydrogen bonding, etc.) due to their chemical diversity, allowing the enantio-separation of analytes with a wide range of structural characteristics. This article aims to review the application of various classes of antibiotics in the CE enantio-separation of pharmaceuticals. Antibiotic physiochemical characteristics, variables impacting enantio-separation, advantages, and disadvantages when certain antibiotics are used as CSs in CE are also explored.

Determination of Chiral Impurity of Naproxen in Different Pharmaceutical Formulations Using Polysaccharide-Based Stationary Phases in Reversed-Phased Mode.

A novel, validated, reversed-phase (RP), chiral high performance liquid chromatography (HPLC) method was developed for the enantiopurity control analysis of naproxen, a frequently used non-steroidal anti-inflammatory agent using polysaccharide-type chiral stationary phase (CSP). In the screening phase of method development, seven columns were tested in polar organic (PO) mode using mobile phases consisting of 0.1% acetic acid in methanol, ethanol, 2-propanol, and acetonitrile. Enantiorecognition was observed only in five cases. The best enantioseparation was observed on a Lux Amylose-1 column with 0.1% (v/v) acetic acid in ethanol with a resolution (Rs) of 1.24. The enantiomer elution order was unfavorable, as the distomer eluted after the eutomer. When the ethanolic mobile phase was supplemented with water, enantiomer elution order reversal was observed, indicating a difference in the enantiorecognition mechanism upon switching from PO to RP mode. Furthermore, by changing ethanol to methanol, not only lower backpressure, but also higher resolution was obtained. Subsequent method optimization was performed using a face-centered central composite design (FCCD) to achieve higher chiral resolution in a shorter analysis time. Optimized parameters offering baseline separation were as follows: Lux Amylose-1 stationary phase, thermostated at 40 °C, and a mobile phase consisting of methanol:water:acetic acid 85:15:0.1 (v/v/v), delivered with 0.65 mL/min flow rate. Using these optimized parameters, a Rs = 3.21 ± 0.03 was achieved within seven minutes. The optimized method was validated according to the ICH guidelines and successfully applied for the analysis of different pharmaceutical preparations, such as film-coated tablets and gel, as well as fixed-dose combination tablets, containing both naproxen and esomeprazole.

Photosensitivity Reactions Induced by Photochemical Degradation of Drugs.

Photochemical degradation of drugs can lead to degradation products with potential toxic or allergizing effects for the human body. A significant amount of work has been carried out over the past few decades to clarify the molecular mechanism of photosensitizing processes observed after the administration of certain drugs and exposure to light. There is a close relation between the photosensitizer effect of a drug and its chemical structure. Compounds possessing certain moieties and functional groups in their molecular structure, like aromatic chromophore systems or photo-dissociable bonds that can form free radicals, and consequently are susceptible to have light-induced adverse effects. Photoionization, photodissociation, photoaddition and photoisomerization are the main chemical processes, which can occur during the photochemical decomposition of a pharmaceutical compound. The current study is a short review describing photochemical degradation of certain pharmaceuticals, presenting specific examples from various pharmaceutical classes for the different types of decomposition mechanisms. In vivo methods and clinical tests available for the investigation of photosensitizing reactions are also discussed.

Chiral Switch: Between Therapeutical Benefit and Marketing Strategy.

Chirality of pharmaceutical substances is an important aspect in drug research because it determines how enantiomers will interact with chiral biological targets. Enantiomers of a chiral drug can have different pharmacokinetic and pharmacological profiles; consequently, using a single pure enantiomer instead of a racemate can enhance the effectiveness and/or safety of the treatment. The tendencies of modern pharmaceutical industry regarding the current market of chiral drugs are divided between the chiral switch of previously used racemates and the development of new enantiopure drugs. The term chiral switch refers to the replacement on the market of a previously approved racemate with its single enantiomer version. The potential advantages of chiral switch can be related to a higher therapeutic index due to better potency, selectivity and fewer adverse effects, faster onset of action and exposure of the patient to lower drug dosages. However, chiral switch is also a strategy that permits manufacturers to keep market exclusivity for chiral pharmaceuticals that have lost their patent protection, even if the pure enantiomers have not demonstrated higher effectiveness or safety profile compared with the racemates.

Structural Characterization of the Millennial Antibacterial (Fluoro)Quinolones-Shaping the Fifth Generation.

The evolution of the class of antibacterial quinolones includes the introduction in therapy of highly successful compounds. Although many representatives were withdrawn due to severe adverse reactions, a few representatives have proven their therapeutical value over time. The classification of antibacterial quinolones into generations is a valuable tool for physicians, pharmacists, and researchers. In addition, the transition from one generation to another has brought new representatives with improved properties. In the last two decades, several representatives of antibacterial quinolones received approval for therapy. This review sets out to chronologically outline the group of approved antibacterial quinolones since 2000. Special attention is given to eight representatives: besifloxacin, delafoxacin, finafloxacin, lascufloxacin, nadifloxacin and levonadifloxacin, nemonoxacin, and zabofloxacin. These compounds have been characterized regarding physicochemical properties, formulations, antibacterial activity spectrum and advantageous structural characteristics related to antibacterial efficiency. At present these new compounds (with the exception of nadifloxacin) are reported differently, most often in the fourth generation and less frequently in a new generation (the fifth). Although these new compounds' mechanism does not contain essential new elements, the question of shaping a new generation (the fifth) arises, based on higher potency and broad spectrum of activity, including resistant bacterial strains. The functional groups that ensured the biological activity, good pharmacokinetic properties and a safety profile were highlighted. In addition, these new representatives have a low risk of determining bacterial resistance. Several positive aspects are added to the fourth fluoroquinolones generation, characteristics that can be the basis of the fifth generation. Antibacterial quinolones class continues to acquire new compounds with antibacterial potential, among other effects. Numerous derivatives, hybrids or conjugates are currently in various stages of research.

Application of Experimental Design Methodologies in the Enantioseparation of Pharmaceuticals by Capillary Electrophoresis: A Review.

Chirality is one of the major issues in pharmaceutical research and industry. Capillary electrophoresis (CE) is an interesting alternative to the more frequently used chromatographic techniques in the enantioseparation of pharmaceuticals, and is used for the determination of enantiomeric ratio, enantiomeric purity, and in pharmacokinetic studies. Traditionally, optimization of CE methods is performed using a univariate one factor at a time (OFAT) approach; however, this strategy does not allow for the evaluation of interactions between experimental factors, which may result in ineffective method development and optimization. In the last two decades, Design of Experiments (DoE) has been frequently employed to better understand the multidimensional effects and interactions of the input factors on the output responses of analytical CE methods. DoE can be divided into two types: screening and optimization designs. Furthermore, using Quality by Design (QbD) methodology to develop CE-based enantioselective techniques is becoming increasingly popular. The review presents the current use of DoE methodologies in CE-based enantioresolution method development and provides an overview of DoE applications in the optimization and validation of CE enantioselective procedures in the last 25 years. Moreover, a critical perspective on how different DoE strategies can aid in the optimization of enantioseparation procedures is presented.

Chiral separation in the class of proton pump inhibitors by chromatographic and electromigration techniques: An overview.

Proton pump inhibitors (PPIs) are benzimidazole-derivative chiral sulfoxides, frequently used in the treatment of gastric hyperacidity-related disorders. Due to their stereoselective metabolism, the eutomeric forms of PPIs can present a more advantageous pharmacokinetic profile by comparison with the distomers or racemates. Moreover, two representatives of the class are used in therapy both as racemates and as pure enantiomers (esomeprazole, dexlansoprazole). A relatively large number of enantioseparation methods employed for the stereoselective determination of PPIs from pharmaceutical, biological, and environmental matrices were published in the past three decades. The purpose of the current overview is to provide a systematic survey of the available chiral separation methods published since the introduction of PPIs in the therapy up to the present. Analytical and bioanalytical methods using different chromatographic and electromigration techniques reported for the enantioseparation of omeprazole, lansoprazole, pantoprazole, rabeprazole, ilaprazole, and tenatoprazole are included. The analytical conditions of the presented methods are summarized in three comprehensive tables, while a critical discussion of the applied techniques, possible mechanism of enantiorecognition, and future perspectives on the topic are also presented.

The Use of Dual Cyclodextrin Chiral Selector Systems in the Enantioseparation of Pharmaceuticals by Capillary Electrophoresis: An Overview.

Cyclodextrin (CD) derivatives are the most efficient and frequently used chiral selectors (CSs) in capillary electrophoresis (CE). There are situations when the use of a single CD as CS is not enough to obtain efficient chiral discrimination of the enantiomers; in these cases, sometimes this problem can be resolved using a dual CD system. The use of dual CD systems can often dramatically enhance enantioseparation selectivity and can be applied for the separation of many analytes of pharmaceutical interest for which enantioseparation by CE with another CS systems can be problematic. Usually in a dual CD system an anionic CD is used together with a neutral one, but there are situations when the use of a cationic CD with a neutral one or the use of two neutral CDs or even two ionized CDs can be an efficient solution. In the current review we present general aspects of the use of dual CD systems in the analysis of pharmaceutical substances. Several examples of applications of the use of dual CD systems in the analysis of pharmaceuticals are selected and discussed. Theoretical aspects regarding the separation of enantiomers through simultaneous interaction with the two CSs are also explained. Finally, advantages, disadvantages, potential and new direction in this chiral analysis field are highlighted.