Enantioseparation of chiral ß-blockers using polynorepinephrine-coated nanoparticles and chiral capillary electrophoresis.

A method of combining magnetic solid-phase separation (MSPE) and chiral capillary electrophoresis (CE) is developed for enantioseparation of trace amounts of ß-blockers. Polynorepinephrine-functionalized magnetic nanoparticles (polyNE-MNPs) are synthesized and applied to simultaneously extract three ß-blockers (carteolol, metoprolol, and betaxolol). The prepared polyNE-MNPs are spherical with a diameter of 198 ± 17 nm and the thickness of the polyNE coating is about 14 nm. PolyNE possesses abundant catechol hydroxyl and secondary amine groups, endowing the MNPs with excellent hydrophilicity. Under the optimum conditions, the extraction efficiencies of polyNE-MNPs for ß-blockers are in the range of 89.6 to 100%, with relative standard deviations (RSDs) below 3.5%. The extraction process can be finished in 4 min. Field-enhanced sample injection (FESI) in chiral CE is constructed to further enhance the sensitivities of ß-blocker enantiomers. The limits of detection for ß-blocker enantiomers by the FESI-CE with polyNE-MNPs are in the range of 0.401 to 1.59 ng mL-1. The practicability of this method in real samples is evaluated by analysis of human urine samples. The recoveries for each enantiomer of ß-blockers in the real samples range from 89.5 to 92.8%, with RSDs ranging from 0.37 to 5.9%. The whole detection process can be finished in less than 0.5 h. The method demonstrates its great potential in the pharmacokinetic and pharmacodynamic studies of chiral drugs in humans. Graphical abstract ᅟ.

Box-Behnken response surface modeling assisted enantiomeric resolution of some racemic ß-blockers using HPTLC and ß-cyclodextrin as chiral mobile phase additive: Application to check the enantiomeric purity of betaxolol.

Stereospecific separation method of (±) betaxolol, (±) carvedilol, and (±) sotalol using High Performance Thin Layer Chromatography (HPTLC) and ß-cyclodextrin as chiral selector has been developed and validated. The Box-Behnken surface response design was selected for optimizing the operating variables based on 15 trials design. The optimized method involves separation on Fluka HPTLC silica gel plates 60 F254 (20 × 10 cm) using acetonitrile-methanol-acetic acid-water (3.4:3.6:0.18:1 v/v) as a mobile phase containing 0.57 mM ß-cyclodextrin. Densitometric measurements were made at 220 nm for betaxolol and sotalol or at 245 nm for carvedilol. Maximum separation of the enantiomers of the three drugs was obtained by optimizing concentration of chiral selector, the mobile phase composition including acetonitrile amount in the organic part of the mobile phase and the volume of acetic acid added. The proposed method enables estimation of (-) and (+) enantiomers of betaxolol in drug substance and in various pharmaceuticals. The detection limit of betaxolol was 0.15 and 0.13 µg band-1 for (-) and (+) enantiomers, respectively. The detection limits were found to be 0.2 and 0.3 µg band-1 for carvedilol and sotalol, respectively, as racemate. In addition, the proposed method was applied in checking the enantiomeric purity of (-) BET in the presence of (+) BET at 1% level where the inactive (+) enantiomer was quantified with good accuracy and precision at 1% level in the active (-) enantiomer.

On-line coupling of Micro-Extraction by Packed Sorbent with Sequential Injection Chromatography system for direct extraction and determination of betaxolol in human urine.

A novel approach for automation of Micro-Extraction by Packed Sorbent (MEPS), a solid phase extraction technique, is presented, enabling precise and repeatable liquid handling due to the employment of sequential injection technique. The developed system was used for human urine sample clean-up and pre-concentration of betaxolol before its separation and determination. A commercial MEPS C-18 cartridge was integrated into an SIChrom™ system. The chromatographic separation was performed on a monolithic High Resolution C18 (50×4.6 mm) column which was coupled on-line in the system with Micro-Extraction using an additional selection valve. A mixture of acetonitrile and aqueous solution of 0.5% triethylamine with acetic acid, pH adjusted to 4.5 in ratio 30:70 was used as a mobile phase for elution of betaxolol from MEPS directly onto the monolithic column where the separation took place. Betaxolol was quantified by a fluorescence detector at wavelengths λ(ex)=220 nm and λ(em)=305 nm. The linear calibration range of 5-400 ng mL(-1), with limit of detection 1.5 ng mL(-1) and limit of quantification 5 ng mL(-1) and correlation r=0.9998 for both the standard and urine matrix calibration were achieved. The system recovery was 105±5%; 100±4%; 108±1% for three concentration levels of betaxolol in 10 times diluted urine - 5, 20 and 200 ng mL(-1), respectively.

Multivariate curve resolution-alternating least squares assisted by voltammetry for simultaneous determination of betaxolol and atenolol using carbon nanotube paste electrode.

In the present work differential pulse voltammetry coupled with multivariate curve resolution-alternating least squares (MCR-ALS) was applied for simultaneous determination of betaxolol (Bet) and atenolol (Ate) in 0.20 M Britton-Robinson (B-R) buffer solution at the surface of a multi-walled carbon nanotube modified carbon paste electrode (MWCNT/CPE). Characterization of the modified electrode was carried out by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). A strategy based on experimental design was followed. Operating conditions were improved with central composite rotatable design (CCRD) and response surface methodology (RSM), involving several chemical and instrumental parameters. Then second order data were built from variable pulse heights of DPV and after correction in potential shift analyzed by MCR-ALS. Analytical parameters such as linearity, repeatability, and stability were also investigated and a detection limit (DL) of 0.19 and 0.29 µM for Bet and Ate was achieved, respectively. The proposed method was successfully applied in simultaneous determining the two analytes in human plasma.