Highly exfoliated functionalized MoS2 with sodium alginate-polydopamine conjugates for electrochemical sensing of cardio-selective ß-blocker by voltammetric methods.

Molybdenum disulfide (MoS2) surface functionalization was performed with a catechol-containing polymer sodium alginate (SA) and dopamine (DA) through simultaneous MoS2 exfoliation and self-polymerization of DA. The MoS2/SA-PDA nanocomposite was characterized using spectroscopic, microscopic, and electroanalytical techniques to evaluate its electrocatalytic performance. The electrocatalytic behavior of the MoS2/SA-PDA nanocomposite modified electrode for the detection of acebutolol (ACE), a cardio-selective ß-blocker drug was explored  through cyclic voltammetric and differential pulse voltammetric techniques. The influence of scan rate, concentration, and pH value on the oxidation peak current of ACE was investigated  to optimize the deducting condition. The electrochemical activity of the MoS2/SA-PDA nanocomposite electrode was attributed to the existence of reactive functional groups being contributed from SA, PDA, and MoS2 exhibiting a synergic effect. The MoS2/SA-PDA nanocomposite modified electrode exhibits admirable electrocatalytic activity with a wide linear response range (0.009 to 520 µM), low detection limit (5 nM), and high sensitivity (0.354 µA µM-1 cm-2) also in the presence of similar (potentially interfering) compounds. The fabricated MoS2/SA-PDA nanocomposite modified electrode can be useful for the detection of ACE in pharmaceutical analysis.

Chiral separation of beta-blockers by high-performance liquid chromatography and determination of bisoprolol enantiomers in surface waters.

Beta-blockers are chiral compounds with enantiomers that have different bioactivity, which means that while one is active, the other can be inactive or even harmful. Due to their high consumption and incomplete degradation in waste water, they may reach surface waters and affect aquatic organisms. To address this issue we developed a chromatographic method suitable for determining beta-blocker enantiomers in surface waters. It was tested on five beta-blockers (acebutolol, atenolol, bisoprolol, labetalol and metoprolol) and validated on bisoprolol enantiomers. Good enantioseparation of all analysed beta-blockers was achieved on the Chirobiotic V column with the mobile phase composed of methanol/acetic acid/triethylamine (100/0.20/0.15 v/v/v) at a flow rate of 0.5 mL/min and column temperature of 45 °C. Method proved to be linear in the concentration range from 0.075 µg/mL to 5 µg/mL, and showed good recovery. The limits of bisoprolol enantiomer detection were 0.025 µg/mL and 0.026 µg/mL and of quantification 0.075 µg/mL and 0.075 µg/mL. Despite its limitations, it seems to be a promising method for bisoprolol enantiomer analysis in surface water samples. Further research could focus on waste water analysis, where enantiomer concentrations may be high. Furthermore, transferring the method to a more sensitive one such as liquid chromatography coupled with tandem mass spectrometry and using ammonium acetate as the mobile phase additive instead of acetic acid and triethylamine would perhaps yield much lower limits of detection and quantification.

Analysis of 27 ß-Blockers and Metabolites in Milk Powder by High Performance Liquid Chromatography Coupled to Quadrupole Orbitrap High-Resolution Mass Spectrometry.

This paper presents an application of high performance liquid chromatography coupled with quadrupole orbitrap high-resolution mass spectrometry (HPLC-Q-Orbitrap HRMS) for the analysis of 27 ß-blockers and metabolites in milk powder. Homogenized milk power samples were extracted by acetonitrile and purified by using Oasis PRiME HLB solid-phase extraction cartridges. The Ascentis® C8 chromatographic column was used to separate the analytes. The quantification was achieved by using matrix-matched standard calibration curves with carazolol-d7 and propranolol-d7 as the internal standards. The results show an exceptional linear relationship with the concentrations of analytes over wide concentration ranges (0.5⁻500 µg kg-1) as all the fitting coefficients of determination r² are > 0.995. All the limits of detection (LODs) and quantitation (LOQs) values were within the respective range of 0.2⁻1.5 µg kg-1 and 0.5⁻5.0 µg kg-1. Overall average recoveries were able to reach 66.1⁻100.4% with the intra- and inter-day variability under 10%. This method has been successfully applied to the screening of ß-blockers and metabolites in commercial milk powders. At the same time, the corresponding characteristic fragmentation behavior of the 27 compounds was explored. The characteristic product ions were determined and applied to the actual samples screening.

1H and 13C NMR characteristics of ß-blockers.

The ß-blockers are important drugs and decades of clinical experience proved their high medical status. However, to the best of our knowledge, there is no complete assignment of (1)H and (13)C NMR resonances of popular representatives: acebutolol, alpenolol, pindolol, timolol and propranolol and the published NMR data on carvedilol and atenolol are incorrect. Therefore, (1)H and (13)C NMR spectroscopy was applied for the characterization of a series of ß-adrenolytics: carvedilol (1), pindolol (2), alprenolol (3), acebutolol (4), atenolol (5), propranolol (6) and timolol (7). Two-dimensional NMR experiments (COSY, HMQC, HMBC, NOESY) allowed the unequivocal assignment of (1)H and (13)C spectra for solution (DMSO-d(6) ). Salts and bases can be easily distinguished based on (13)C chemical shifts which are within 65.0-65.5 ppm (OC2) and 46.9-47.0 (NC3) for hydrochlorides and larger, ca. 68.4 ppm (OC2) and 50.3-52.6 (NC3) for bases. NMR data of 1-7 should be included in pharmacopoeias.

Determination of selected beta-receptor antagonists in biological samples by solid-phase extraction with cholesterolic phase and LC/MS.

A new method is presented for the determination of five selected beta-receptor antagonists by HPLC, which emphasizes sample preparation via retention on a new type of silica gel sorbent used for solid-phase extraction (SPE). Sorbents of this type were obtained by the chemical modification of silica gels of various porosities by cholesterol ligands. The cholesterol-based packing material was investigated by spectroscopic methods and elemental analysis. The recoveries obtained with the extraction procedure were optimum over a relatively broad sample pH range (3.08-7.50). Analytical factors such as the sample loading, the washing step and elution conditions, the concentration of beta-receptor antagonists to be extracted, and the type of sorbent were found to play significant roles in the sample preparation procedure and would therefore need to be controlled to achieve optimum recoveries of the analytes. Under optimum conditions, the recoveries of nadolol, acebutolol, esmolol, oxprenolol and propranolol from spiked buffers, blood and urine were reproducible and dependent on the polarity or hydrophilicity of the compounds. The above analytes were determined by reverse-phase high-performance liquid chromatography (HPLC) with UV and ESI-ion trap mass spectrometry (MS) detection. The described method was found to be suitable for the routine measurement of compounds that are both polar and basic, and can be applied for the analysis of biological samples such as urine and blood in clinical, toxicological or forensic laboratories. The recovery measurements were performed on spiked human urine and serum, and on real samples of mouse blood serum.

Spectrophotometric and spectrofluorimetric methods for analysis of acyclovir and acebutolol hydrochloride.

Simple and sensitive spectrophotometric and spectrofluorimetric methods are described for analysis of acyclovir and acebutolol hydrochloride. The proposed methods are based on oxidation of the selected drugs with cerium(IV) ion in acidic medium with subsequent measurement of either the decrease in absorbance at 320nm or the fluorescence intensity of the produced cerous(III) ion at 361-363nm (excitation at 250nm). Beer's law obeyed from 2 to 8, 0.25 to 2.5microgcm-1 acyclovir, 1 to 7 and 0.25 to 2.5microgml-1 acebutolol hydrochloride, using the spectrophotometric and spectrofluorimetric method, respectively. The proposed method were successfully applied for determination of the selected drugs in their pharmaceutical preparations with good recoveries.

Spectrophotometric and spectrofluorimetric methods for analysis of acyclovir and acebutolol hydrochloride.

Simple and sensitive spectrophotometric and spectrofluorimetric methods are described for analysis of acebutolol hydrochloride. The proposed methods are based on oxidation of the selected drug with cerium(IV) ion in acidic medium with subsequent measurement of either the decrease in absorbance at 320 nm or the fluorescence intensity of the produced cerous(III) ion at 363 nm (excitation at 250 nm). Beer's law obeyed from 1.0-7.0 microg ml(-1) and 0.25-2.5 microg ml(-1) acebutolol hydrochloride, using the spectrophotometric and spectrofluorimetric method, respectively. The proposed methods were successfully applied for determination of the selected drug in its pharmaceutical preparation with good recoveries.

Spectrofluorimetric determination of drugs containing active methylene group using N1-methyl nicotinamide chloride as a fluorigenic agent.

A spectrofluorimetric method was described for the determination of drugs containing active methylene groups adjacent to carbonyl groups. The method was applied successfully to the determination of three life saving cardiovascular drugs, with narrow therapeutic indices: pentoxifylline (I), propafenone hydrochloride (II) and acebutolol hydrochloride (III), in laboratory-prepared mixtures, in commercial tablets and in plasma samples. The method involved the reaction of each of the tested drugs with N1-methyl nicotinamide chloride (NMNCl) in the presence of alkali, followed by addition of formic acid, where highly fluorescent reaction products were produced. The produced fluorescence were measured quantitatively at 472 nm (lambdaex 352 nm), 409 nm (lambdaex 310 nm) and 451 nm (lambdaex 266 nm) for (I), (II), and (III) respectively. The method was linear over concentration ranges of 10-1000 microg/ml , 0.2-12 microg/ml and 0.08-10 microg/ml in standard solutions for (I), (II), and (III) respectively. In spiked human plasma samples, calibration graphs were linear over concentration ranges of 20-1000 microg/ml, 0.2-15 microg/ml and 0.08-10 microg/ml for (I), (II), and (III) respectively. The method showed good accuracy, specificity and precision in both laboratory-prepared mixtures and spiked human plasma samples. The proposed method is simple, with low instrumentation requirements, suitable for quality control application, bioavailability and bioequivalency studies.

Spectrophotometric and spectrofluorimetric methods for analysis of tramadol, acebutolol and dothiepin in pharmaceutical preparations.

Sensitive spectrophotometric and spectrofluorimetric methods are described for the determination of tramadol, acebutolol and dothiepin (dosulepin) hydrochlorides. The two methods are based on the condensation of the cited drugs with the mixed anhydrides of malonic and acetic acids at 60 degrees C for 25-40 min. The coloured condensation products are suitable for the spectrophotometric and spectrofluorimetric determination at 329-333 and 431-434 nm (excitation at 389 nm), respectively. For the spectrophotometric method, Beer's law was obeyed from 0.5 to 2.5 microg ml(-1) for tramadol, dothiepin and 5-25 microg ml(-1) for acebutolol. Using the spectrofluorimetric method linearity ranged from 0.25 to 1.25 microg ml(-1) for tramadol, dothiepin and 1-5 microg ml(-1) for acebutolol. Mean percentage recoveries for the spectrophotometric method were 99.68+/-1.00, 99.95+/-1.11 and 99.72+/-1.01 for tramadol, acebutolol and dothiepin, respectively and for the spectrofluorimetric method, recoveries were 99.5+/-0.844, 100.32+/-0.969 and 99.82+/-1.15 for the three drugs, respectively. The optimum experimental parameters for the reaction has been studied. The validity of the described procedures was assessed. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The proposed methods were successfully applied for the determination of the selected drugs in their pharmaceutical preparations with good recoveries. The procedures were accurate, simple and suitable for quality control application.

Assay of acebutolol in pharmaceuticals by analytical capillary isotachophoresis.

Acebutolol [N-{3-acetyl-4-[(2-hydroxy-3-(isopropylamino)propoxy]phenyl} butanamide] is a cardioselective beta-blocker with a potent anti-hypertensive and antiarrhythmic effect. The optimised operational system of electrolytes for the newly developed ITP separation of acebutolol consisted of 10mM potassium acetate +10mM acetic acid (pH 4.65) as the leading electrolyte and 10mM beta-alanine with pH approximately 4 (adjusted with acetic acid) as the terminating electrolyte. The driving and detection currents were 75 and 20 microA, respectively and the analysis took approximately 13 min. Under these conditions the effective mobility of acebutolol was determined as 20.7 x 10(-9) m2 V(-1) s(-1). The calibration dependence was rectilinear in the range 0.14-1.4 mg ml(-1) of acebutolol base (r = 0.9995); relative standard deviation (RSD) values were 1.1% and 1.2% (n = 6) when determining 0.42 and 0.98 mg ml(-1) of acebutolol in a pure standard solution. The method, with the limit of detection (LOD) of 0.04 mg ml(-1) and limit of quantification (LOQ) of 0.12 mg ml(-1), was applied to the assay of acebutolol in Sectral tablets, Acecor tablets, Apo-acebutol tablets (nominal content 400 mg of acebutolol per tablet) and Acebirex tablets (nominal content 200 mg of acebutolol per tablet) with RSD = 0.7-1.7% (n = 6). No interference from any excipients present in the tablets was observed. The recoveries ranged from 98.8% to 102.4% as found by the standard addition technique.

Sleep-deprived mice show altered cytokine production manifest by perturbations in serum IL-1ra, TNFa, and IL-6 levels.

Serum cytokine and chemokine levels were examined in mice following 36 h of sleep deprivation, or after exposure to a known physical stressor (rotational stress). Significant changes in inflammatory cytokines/chemokines (IL-1beta, TNFalpha, IL-1ra, IL-6, and MIP-1beta, MCP-1) were observed following each manipulation, but qualitative and quantitative differences were seen. Interestingly, only physical stress was associated with measured increases in serum corticosterone levels, and with independent evidence (using in vitro immune allostimulation) for a generalized immunosuppression secondary to the experimental manipulation. Our data suggest that altered cytokine production following sleep perturbation occurs by a different mechanism from that (HPA axis) commonly attributed to stress per se.

First derivative spectrophotometric, TLC-densitometric, and HPLC determination of acebutolol HCL in presence of its acid-induced degradation product.

Three methods are presented for the determination of acebutolol HCl in presence of its acid-induced degradation product. The first method was based on measurement of the first derivative amplitude of acebutolol HCl at 266.6 nm. The second method was based on separation of acebutolol HCl from its acid-induced degradation product followed by densitometric measurement of the spots at 230 nm. The separation was carried out on silica gel 60 F254, using ethanol-glacial acetic acid (4:1, v/v) as mobile phase. Second order polynomial equation was used for the regression line. The third method was based on high performance liquid chromatographic (HPLC) separation of acebutolol HCl from its acid-induced degradation product on a reversed phase, ODS column using a mobile phase of methanol-water (55:45, v/v) with UV detection at 240 nm. The first derivative spectrophotometric method was utilized to investigate the kinetics of the acid degradation process at different temperatures.

Evaluation of the immobilized artificial membrane phosphatidylcholine. Drug discovery column for high-performance liquid chromatographic screening of drug-membrane interactions.

Chromatographic retention factors (k') of a series of eight beta-adrenoceptor antagonist compounds (beta-adrenolytic drugs) were determined employing an immobilized artificial membrane column (IAM.PC.DD). The influence of mobile phase pH, ionic strength, and organic modifier composition was studied in order to examine column performance. After the IAM.PC.DD columns were exposed to approximately 7000 column volumes of a 0.01 M PBS mobile phase, five out of six columns tested showed significant peak broadening and decreased k' values indicative of premature column failure. The data suggested that the immobilized phospholipids stationary phase was removed by the 0.01 M PBS mobile phase. The beta-adrenolytic drug's log k'IAM values obtained with an IAM.PC.DD column were compared to an esterIAM.PC.MG column for predicting drug membrane interactions. For the linear regression analysis between log k'IAM and the logarithm of the n-octanol-water partition coefficients (rIAM.PC.DD = 0.8710 vs. rIAM.PC.MG = 0.9538), the C18 HPLC retention factors (rIAM.PC.DD = 0.8408 vs. rIAM.PC.MG = 0.9380), the liposome partition coefficients (rIAM.PC.DD = 0.8887 vs. rIAM.PC.MG = 0.9187), and various pharmacokinetic parameters, significantly better correlations were obtained with the esterIAM.PC.MG column than the IAM.PC.DD column.

Analysis of nifedipine-acebutolol hydrochloride binary combination in tablets using UV-derivative spectroscopy, capillary gas chromatography and high performance liquid chromatography.

Three methods are described for the simultaneous determination of nifedipine and acebutolol hydrochloride in combined pharmaceutical tablets. The first method depends on first-derivative ultraviolet spectrophotometry, with peak-to-base and zero-crossing measurements methods. The first derivative amplitudes at 400 and 352 nm were selected for the assay of nifedipine and acebutolol hydrochloride, respectively. Calibration graphs follow Beer's law in the range of 4-12 and 44-132 micrograms ml-1 and the linearity was satisfactory (r = 0.999) for nifedipine and acebutolol hydrochloride, respectively. The second method was based on the separation of nifedipine from acebutolol hydrochloride, with an internal standard thymolphthalein, using capillary gas-liquid chromatography with a programmable temperature change. The third method was based on high performance liquid chromatographic separation of the two drugs on a reversed-phase, C18, column using a mobile phase of methanol-water (55:45, pH 4.5) with a programmable flow rate of 1 ml min-1 for 4 min which changed to 2 ml min-1 for the rest of the run. The detection was done at 260 nm using oxprenolol hydrochloride as an internal standard. Both chromatographic methods showed good linearity, precision and reproducibility. No spectral or chromatographic interference from the tablet excipients were found. The proposed methods were successfully applied to the assay of commercial tablets and a content uniformity test. The procedures were rapid, simple nondestructive and suitable for quality control application.

Toxicological findings in a fatal case of acebutolol self-poisoning.

A fatal case of acebutolol self-poisoning is presented. After single-step liquid-liquid alkaline extraction, acebutolol was identified by using an HPLC/DAD screening procedure. By means of a specific HPLC method, acebutolol was then quantified in a large range of postmortem samples. The blood acebutolol concentration was 34.7 micrograms/mL. The tissue distribution of the drug is discussed in the light of the existing literature.

[Acebutolol and diacetolol: their binding to plasma proteins and erythrocytes and secretion with the saliva]. / Atsebutolol i diatsetolol: sviaz' s belkami plazmy i éritrotsitami, sekretsiia so sliunoi.

Thirty-two patients with hypertensive disease were treated with a cardioselective blocker of beta-adrenergic receptors acebutolol ("Sectral-400", Rhone Poulenc, France). The binding of the drug and its metabolites diacetolol to plasma proteins and erythrocytes and their excretion with the saliva were studied. The significant binding of acebutolol and diacetolol to erythrocytes was shown. The ratio of the content of the free form of these substances in erythrocytes to plasma content was on the average 1.54 +/- 0.96 for diacetolol and 1.93 +/- 1.01 for acebutolol. A good correlation of acebutolol and diacetolol contents in the saliva with their contents in plasma was found. The mean values of the protein-bound fraction were for acebutolol 0.133 +/- 0.038 and for diacetolol 0.106 +/- 0.050.

[Absorption and fluorescence spectrometry measurement of intraocular lenses]. / Absorptions- und fluoreszenzspektrometrische Messungen an Intraokularlinsen.

Light absorption and fluorescence measurements can be used to detect accumulations of small molecules in intraocular lenses (IOLs). It was shown that HEMA IOLs can store and to some extent release a variety of drugs and fluorescein. PMMA and silicone IOLs, however, do not have this characteristic. UV-blocking IOLs absorb UV light completely. The absorption limit varies between 390 and 410 nm, depending on the make. Neither absorption nor fluorescence response were affected by exposure to UV light or heat.

Reversed-phase high-performance liquid chromatography with differential pulse polarographic detection for assaying drugs in feed: stability-indicating assay of diacetolol.

Reversed-phase high-performance liquid chromatography with differential pulse polarographic detection at a dropping mercury electrode provides a high degree of specificity for stability-indicating assays of drugs in animal feed. The selectivity of this detection system is demonstrated in the assay of diacetolol in feed at concentrations down to 50 microgram/g.