Metal organic framework HKUST-1 modified with carboxymethyl-ß-cyclodextrin for use in improved open tubular capillary electrochromatographic enantioseparation of five basic drugs.

This work shows that the metal organic framework (MOF) HKUST-1 of type Cu3(BTC)2 (also referred to as MOF-199; a face-centered-cubic MOF containing nanochannels) is a most viable coating for use in enantioseparation in capillary electrochromatography (CEC). A HKUST-1 modified capillary was prepared and characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectra, elemental analysis and thermogravimetric analysis. CEC-based enantioseparation of the basic drugs propranolol (PRO), esmolol (ESM), metoprolol (MET), amlodipine (AML) and sotalol (SOT) was performed by using carboxymethyl-ß-cyclodextrin as the chiral selector. Compared with a fused-silica capillary, the resolutions are improved (ESM: 1.79; MET: 1.80; PRO: 4.35; SOT: 1.91; AML: 2.65). The concentration of chiral selector, buffer pH value, applied voltage and buffer concentration were optimized, and the reproducibilities of the migration times and Rs values were evaluated. Graphical abstract Schematic presentation of the preparation of a HKUST-1@capillary for enantioseparation of racemic drugs. Cu(NO3)2 and 1,3,5-benzenetricarboxylic acid (BTC) were utilized to prepare the HKUST-1@capillary. Then the capillary was applied to construct capillary electrochromatography system with carboxymethyl-ß-cyclodextrin (CM-ß-CD) for separation of basic racemic drugs.

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.

A multi-walled carbon nanotube-based magnetic molecularly imprinted polymer as a highly selective sorbent for ultrasonic-assisted dispersive solid-phase microextraction of sotalol in biological fluids.

A modified multiwalled carbon nanotube-based magnetic molecularly imprinted polymer (MWCNT-MMIP) was synthesized and applied for selective extraction and preconcentration of sotalol (SOT) in biological fluid samples by using ultrasonic-assisted dispersive solid-phase microextraction (UA-DSPME). The synthetic particles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) analysis, vibrating sample magnetometry (VSM) and Fourier transform infrared spectroscopy (FTIR). The screening of UA-DSPME was preliminarily performed by Plackett-Burman design (PBD) and, subsequently, central composite design (CCD) under response surface methodology (RSM) was used individually for evaluation of the significant factors and their possible interaction effects on the adsorption process. Batch mode adsorption studies were performed to evaluate the adsorption kinetics, adsorption isotherms, and selective recognition of MWCNT-MMIPs. The adsorption equilibrium of SOT using MWCNT-MMIPs could be well-defined with the Langmuir isotherm model and the maximum adsorption capacity was calculated to be 79.36 mg g-1. Under optimized conditions, the SOT was selectively and effectively extracted in real biological samples and good linearity was obtained with correlation coefficients (R2) over 0.996 and the detection limit (S/N = 3) was 0.31 ng mL-1. The average recoveries of the spiked human urine and plasma samples at four concentration levels of SOT ranged from 94.60-102.50 and 97.40-101.60 percent, respectively, and the relative standard deviation was found to be lower than 4.50%. The results illustrated that the proposed MWCNT-MMIPs@UA-DSPME extraction method coupled with HPLC-UV determination could be applied for sensitive and selective analysis of trace SOT in biological fluid samples.

Facile preparation of polysaccharide-coated capillaries using a room temperature ionic liquid for chiral separations.

In this study, the dissolution of polysaccharides into an ionic liquid was investigated and applied as a coating onto the capillary walls of a fused-silica capillary in open-tubular CEC. The coating was evaluated by examining the chiral separation of two analytes (thiopental, sotalol) with three cellulose derivatives (cellulose acetate, cellulose acetate phthalate, and cellulose acetate butyrate). Baseline separation of thiopental enantiomers was achieved by use of each polysaccharide coating (Rs: 7.0, 8.1, 7.1), while sotalol provided partial resolution (Rs: 0.7, 1.0, 0.9). In addition, reproducibility of the cellulose-coated capillaries was evaluated by estimating the run-to-run and capillary-to-capillary RSD values of the EOF. Both stability and reproducibility were very good with RSD values of less than 7%.

Occurrence and removal of pharmaceuticals and hormones through drinking water treatment.

The occurrence of fifty-five pharmaceuticals, hormones and metabolites in raw waters used for drinking water production and their removal through a drinking water treatment were studied. Thirty-five out of fifty-five drugs were detected in the raw water at the facility intake with concentrations up to 1200 ng/L. The behavior of the compounds was studied at each step: prechlorination, coagulation, sand filtration, ozonation, granular activated carbon filtration and post-chlorination; showing that the complete treatment accounted for the complete removal of all the compounds detected in raw waters except for five of them. Phenytoin, atenolol and hydrochlorothiazide were the three pharmaceuticals most frequently found in finished waters at concentrations about 10 ng/L. Sotalol and carbamazepine epoxide were found in less than a half of the samples at lower concentrations, above 2 ng/L. However despite their persistence, the removals of these five pharmaceuticals were higher than 95%.

Extraction and preconcentration of beta-blockers in human urine for analysis with high performance liquid chromatography by means of carrier-mediated liquid phase microextraction.

A novel method was developed for the analysis of four beta-blockers, namely sotalol, carteolol, bisoprolol, and propranolol, in human urine by coupling carrier-mediated liquid phase microextraction (CM-LPME) to high performance liquid chromatography (HPLC). By adding an appropriate carrier in organic phase, simultaneous extraction and enrichment of hydrophilic (sotalol, carteolol, and bisoprolol) and hydrophobic (propranolol) drugs were achieved. High enrichment factors were obtained by optimizing the compositions of the organic phase, the acceptor solution, the donor solution, the stirring rate, and the extraction time. The linear ranges were from 0.05 to 10.0 mg L(-1) for sotalol and carteolol, and from 0.05 to 8.0 mg L(-1) for bisoprolol and propranolol. The limits of detection (S/N=3) were 0.01 mg L(-1) for sotalol, carteolol, and bisoprolol, and 0.005 mg L(-1) for propranolol. The relative standard deviations were lower than 6%. The developed method exhibited high analyte preconcentration and excellent sample clean-up effects with little solvent consumption and was found to be sensitive and suitable for simultaneous determination of the above four drugs spiked in human urine. Furthermore, the successful analysis of propranolol in real urine specimens revealed that the determination of beta-blockers in human urine is feasible using the present method.

Effect of the nature of the single-isomer anionic CD and the BGE composition on the enantiomeric separation of beta-blockers in NACE.

The separation of ten beta-blockers has been investigated in NACE systems using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-CD (HDMS-beta-CD) and heptakis(2,3-di-O-acetyl-6-O-sulfo)-beta-CD (HDAS-beta-CD). The influence on enantioresolution, mobility difference and selectivity of the nature of both anionic CD and BGE anion as well as their concentrations were studied by means of a multivariate approach. A D-optimal design with 25 experimental points was applied. For all studied analytes, the enantiomeric resolution was shown to be significantly influenced by both CD nature and concentration. Except for two compounds, HDAS-beta-CD was found to give higher enantioresolution values than HDMS-beta-CD. The best enantioseparation for all compounds was achieved in the presence of a high chiral selector concentration and for most of them at a low BGE anion concentration. For each investigated compound, operating conditions leading to the best enantiomeric resolution were deduced. A generic NACE system was then recommended, namely 10 mM ammonium acetate and 40 mM HDAS-beta-CD in methanol acidified with 0.75 M formic acid. This generic system was able to completely resolve the enantiomers of all beta-blockers, with a R(s) value of at least 4. Finally, the optimal conditions obtained modelling resolution, mobility difference and selectivity were compared.

Liquid-phase microextraction based on carrier mediated transport combined with liquid chromatography-mass spectrometry. New concept for the determination of polar drugs in a single drop of human plasma.

Recently, we demonstrated for the first time liquid-phase microextraction (LPME) of polar drugs based on carrier mediated transport. In this new extraction technique, selected analytes were extracted as ion-pairs from small volumes of biological samples, through a thin layer of a water immiscible organic solvent immobilised in the pores of a porous hollow fibre (liquid membrane), and into a microl volume of an acidic aqueous acceptor solution placed inside the lumen of the hollow fibre. In the current paper, this new extraction technique was combined with liquid chromatography-mass spectrometry (LC-MS) for the first time. Carrier mediated LPME was evaluated for several new model drugs (0.01

[Determination of sotalol hydrochloride by reversed-phase high performance liquid chromatography].

An RP-HPLC method for determination and detection of sotalol hydrochloride is described. The baseline separation was achieved on ODS column within 15 minutes by using 0.1% HAc-acetonitrile (80:20, V/V) as mobile phase at a flow rate 1.5 mL/min, and the wavelength was set at 227 nm. The linear range was 5-45 mg/L (r = 0.9991) and the limit of detection was 1 mg/L(S/N > 3). The intra-day and inter-day RSDs were 0.20% and 0.93% respectively.

Temperature-induced inversion of elution order in the enantioseparation of sotalol on a cellobiohydrolase I-based stationary phase.

The effect of temperature on the resolution of (RS)-sotalol by immobilized cellobiohydrolase I (CBH I) was studied between 5 and 40 degrees C and Van 't Hoff plots of ln k versus 1/T were acquired at different pH values of the aqueous mobile phase and in the presence of varying organic cosolvents. The elution order of the enantiomers reverses in the range between 17 and 28 degrees C. Beyond this range, enantioseparations with comparatively high resolution factors are achieved either by decreasing or by increasing the temperature. The composition of the mobile phase influences the "crossover" temperature as well as the character of the global adsorption process of the (R)-(-)-enantiomer. Under certain conditions, (R)-(-)-sotalol exhibits an unusual endothermic adsorption behavior. Its retention time increases with increasing temperature. At room temperature (23 degrees C) the enantiomeric elution order can also be regulated by the solvent additive.