Some thoughts about enantioseparations in capillary electrophoresis

Fanali, Salvatore; Chankvetadze, Bezhan

doi:10.1002/elps.201900144

Cited by 79 publications

(64 citation statements)

References 255 publications

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“…CE is often considered a technique of choice for chiral separations [ 26 , 27 , 28 , 29 ]. This is mainly due to its simplicity, speed of chiral screening and low cost when compared to other separation techniques such as chiral HPLC.…”

Section: Resultsmentioning

confidence: 99%

Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems

Masár

Hradski

Schmid

et al. 2020

IJMS

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Several research disciplines require fast, reliable and highly automated determination of pharmaceutically active compounds and their enantiomers in complex biological matrices. To address some of the challenges of Capillary Electrophoresis (CE), such as low concentration sensitivity and performance degradation linked to the adsorption and interference of matrix components, CE in a hydrodynamically closed system was evaluated using the model compounds Pindolol and Propranolol. Some established validation parameters such as repeatability of injection efficiency, resolution and sensitivity were used to assess its performance, and it was found to be broadly identical to that of hydrodynamically opened systems. While some reduction in separation efficiency was observed, this was mainly due to dispersion caused by injection and it had no impact on the ability to resolve enantiomers of model compounds even when spiked into complex biological matrix such as blood serum. An approximately 18- to 23-fold increase in concentration sensitivity due to the employment of wide bore capillaries was observed. This brings the sensitivity of CE to a level similar to that of liquid chromatography techniques. In addition to this benefit and unlike in hydrodynamically opened systems, suppression of electroosmotic flow, which is essential for hydrodynamically closed systems practically eliminates the matrix effects that are linked to protein adsorption.

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Section: Resultsmentioning

confidence: 99%

Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems

Masár

Hradski

Schmid

et al. 2020

IJMS

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“…Among the established methods of binding studies [24], ACE is well suited to enantiomeric separations [25] and simultaneous binding constant determination [26,27]. ACE offers various separation modes in the field of enantioselective investigation [24,27]. Combinations of CE with equilibrium dialysis and CE with ultrafiltration have been used for binding evaluation of AML [28] and fluoxetine [29], respectively.…”

Section: Introductionmentioning

confidence: 99%

“…HSA can hold positively or negatively net charges, depending on the pH value of the BGE. The common approaches rely on measuring alternations of size, shape, or charge due to the complexation [24,25,27]. In terms of the protein additive in the BGE for a direct separation, ACE is also known as mobility shift-affinity CE (ms-ACE) [30,31].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the enantioselective interaction between selected drug enantiomers and human serum albumin by mobility shift‐affinity capillary electrophoresis

Ratih

Wätzig

Stein

et al. 2020

J of Separation Science

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Mobility shift-affinity capillary electrophoresis was employed for enantioseparation and simultaneous binding constant determination. Human serum albumin was used as a chiral selector in the background electrolyte composed of 20 mM phosphate buffer, pH 7.4. The applied setup supports a high mobility shift since albumin and the drug-albumin complex hold negative net charges, while model compounds of amlodipine and verapamil are positively charged. In order to have an accurate effective mobility determination, the Haarhoff-van der Linde function was utilized. Subsequently, the association constant was determined by nonlinear regression analysis of the dependence of effective mobilities on the total protein concentration. Differences in the apparent binding status between the enantiomers lead to mobility shifts of different extends (α). This resulted in enantioresolutions of Rs = 1.05-3.63 for both drug models. R-(+)-Verapamil (K A 1844 M −1) proved to bind stronger to human serum albumin compared to S-(−)-verapamil (K A 6.6 M −1). The association constant of S-(−)-amlodipine (K A 25 073 M −1) was found to be slightly higher compared to its antipode (K A 22 620 M −1) when applying the racemic mixture. The low measurement uncertainty of this approach was demonstrated by the close agreement of the association constant of the enantiopure S-(−)-form (K A 25 101 M −1).

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“…Some limitations were still present, such as peak broadening, a time-consuming process (approximately 35-60 min running time), hazardous organic solvent consumption (normal-phase HPLC), and F I G U R E 1 Chemical structure of linagliptin suboptimal elution order (a small impurity peak appeared at the tail of the Lina peak). Although CE is considered to be a useful analytical method for chiral separation and drug analysis (high separation efficiency, steady analysis, simple operation and development, and reduced solvent and sample consumption) [8][9][10][11][12][13][14][15][16], no chiral CE method has been reported for Lina. Thus, we developed a CE method for the determination of the enantiomeric impurity of this compound.…”

Section: Introductionmentioning

confidence: 99%

A capillary electrophoresis method for the determination of the linagliptin enantiomeric impurity

Mai

Pham

et al. 2020

J of Separation Science

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Linagliptin is a highly specific, long-acting inhibitor that is used as an orally administrable agent for type-2 diabetes treatment. Because only the R-enantiomer is of clinical use, we developed a capillary electrophoresis method for the determination of the enantiomeric impurity of this compound. Carboxymethyl-β-cyclodextrin was selected as the chiral selector for the separation of linagliptin enantiomers. Design of experiments and desirability functions were used for the analytical optimization, which was focused on understanding and improving the electrophoretic process. The effects of significant parameters (background electrolyte concentration and pH, cyclodextrin concentration, temperature, and voltage) were thoroughly investigated. The complete separation of linagliptin and its enantiomeric impurity with baseline resolution was achieved within 10 min on an uncoated fused-silica capillary (50 μm inner diameter, 365 μm outer diameter, 64.5/56 cm in total/ effective length) maintained at 25 • C, under an applied voltage of 28.0 kV. The background electrolyte contained 70 mM sodium acetate and 4.7 mM carboxymethyl-β-cyclodextrin, and the pH was adjusted to 6.10. The method was validated, and a limit of quantitation of 0.05% for the impurity was estimated.

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Some thoughts about enantioseparations in capillary electrophoresis

Cited by 79 publications

References 255 publications

Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems

Advantages and Pitfalls of Capillary Electrophoresis of Pharmaceutical Compounds and Their Enantiomers in Complex Samples: Comparison of Hydrodynamically Opened and Closed Systems

Investigation of the enantioselective interaction between selected drug enantiomers and human serum albumin by mobility shift‐affinity capillary electrophoresis

A capillary electrophoresis method for the determination of the linagliptin enantiomeric impurity

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