Methods and approaches for determination and enantioseparation of (RS)‐propranolol

Propranolol, a β‐adrenergic receptor antagonist, is a chiral compound that is marketed as a racemate, but only the (S)‐(?)‐enantiomer is responsible for the β‐adrenoceptor blocking activity. Different chromatographic methods have been applied for separation and determination of enantiomers of (RS)‐propranolol. In this article a review is presented on different liquid chromatographic methods used for enantioseparation of (RS)‐propranolol, using both HPLC and TLC. In addition, some aspects of enantioseparation under achiral phases of liquid chromatography have been briefly mentioned.     

Preparation and Evaluation of Propranolol-Imprinted Monolithic Stationary Phase by In Situ Technique and Application in Analysis of Propranolol in Biological Samples

Abstract

A propranolol molecule-imprinted monolithic stationary phase (MIMSP) was synthesized by in situ technique. The recognition mechanism of the polymers and the influences of some chromatographic conditions were examined by high-performance liquid chromatography (HPLC). The imprinted polymers showed much higher selectivity for β-blockers than the nonimprinted polymers (NIPs) did, which proves the successful preparation of propranolol-imprinted polymers by using an in situ technique. Then, this technique was used to prepare a molecularly imprinted polymer solid-phase extraction column to concentrate propranolol from biological samples. The results showed that the imprinted solid-phase extraction column could selectively enrich and purify propranolol from biological samples, such as plasma.     

正相液相色谱-串联质谱法分离普萘洛尔对映体

建立正相液相色谱-串联质谱(LC-MS/MS)分离普萘洛尔对映体的方法,并用于盐酸普萘洛尔片对映体含量测定.样品使用甲醇进行简单提取,采用Chiralcel OD-H手性柱,以正己烷-乙醇-氨水(70∶30∶0.4, v/v/v)为流动相,流速为0.4 mL/min.在正离子模式下,通过电喷雾离子化(ESI+),采用多...     

Hydrophilic interaction liquid chromatographic tandem mass spectrometric determination of atenolol in human plasma

A hydrophilic interaction liquid chromatographic method with tandem mass spectrometry for the determination of atenolol, a beta-blocking agent, in human plasma has been developed and validated over the curve range of 10--2000 ng/mL. The assay was based on protein precipitation followed by evaporation of the extraction solvent, reconstitution with acetonitrile, and chromatography on an Hypersil silica column (50 x 4.6 mm) using a low aqueous--high organic mobile phase. The mobile phase consists of 85% acetonitrile, 15% water, 0.5% acetic acid and 0.04% trifluoroacetic acid and runs isocratically at a flow rate of 2.0 mL/min. The column ef fluent was split so that 50% of it was transferred into the LC-MS/MS interface operated in positive electrospray ionization mode. The chromatographic run time was 2.0 min per injection. Atenolol and the internal standard, atenolol-d(7), showed a retention time of 1.0 min. The inter-day and intra-day precision and accuracy of the quality control samples were <5.3% relative standard deviation and <8.0% relative error, respectively. To explore the application of the current method for the analysis of other beta-blocking agents, propranolol and metoprolol were tested under the same chromatographic conditions with retention times of 0.68 and 0.75 min, respectively. The present method could be used for therapeutic drug monitoring, pharmacokinetic and drug--drug interaction studies of beta-blocking agents.     

A molecular dynamics simulation of the chemisorption of the optical isomers of propranolol on the graphitic electrode modified with melamine,cyanuric, and isocyanuric acids

To demonstrate the nature of the interaction of optical isomers of propranolol with the surface of the graphitic electrode modified with melamine, uracil, cyanuric, and isocyanuric acids, we have performed molecular dynamics simulations of the four‐component systems with variable modifier's molecules. We have considered the possible formation of complexes between the propranolol and modifier's molecules, covering the electrode approximated as the graphene surface. Our simulations demonstrate that the l ‐isomer in aqueous solutions is bonded to the electrode surface stronger than its d ‐counterpart; hence, the difference in analytical signals arises. Different strengths of bonding of the propranolol enantiomers to the surface modifiers are caused by the different intramolecular interactions taking place in the molecules of d ‐ and l ‐isomers. Thus, we have computationally shown that the modification of the graphite surface with melamine, uracil, cyanuric, and isocyanuric acids allows for increasing the sensitivity of the electrode toward the propranolol enantiomers and using the modified graphitic electrodes for the detection of its d ‐ and l ‐forms.     

色谱手性分离研究

以直链淀粉三(3, 5-二甲基苯基氨基甲酸酯)为材料,利用相转化法制备直链淀粉三(3, 5-二甲基苯基氨基甲酸酯)-聚醚砜手性高分子膜. 使用自制的手性膜色谱装置与高效液相色谱仪结合,对手性物质盐酸普萘洛尔和美托洛尔进行了手性膜色谱分离研究. 研究了进样量、流速、膜尺寸对分离效果的影响. 在优选分离效果的条件下,手性膜色谱以纯水为流动相,测得盐酸普萘洛尔的分离因子（α）和分离度（Rs）分别为3.00和0.95,美托洛尔的α和Rs分别为1.65和0.46. 为手性化合物的分离分析开拓了新的途径.     

Molecularly Imprinted Nanospheres by Nonaqueous Emulsion Polymerization

The preparation of nanosized, molecularly imprinted polymer particles by nonaqueous emulsion polymerization is presented. Monodisperse cross‐linked polymer nanospheres with a diameter of around 100 nm were synthesized using a standard monomer mixture of methacrylic acid and ethylene dimethacrylate, containing (±)‐propranolol as a template. The rebinding efficiency of the resulting particles was determined by batch rebinding tests and isothermal titration calorimetry (ITC). The results indicate that the proposed imprinting process under nonaqueous conditions lead to particles with an enhanced capacity of template rebinding compared to both nonimprinted ones and to particles obtained by more conventional emulsion polymerization in water.

     

Borate Complexation and Mixed Cyclodextrin Additives for Chiral Separation of Propranolol and Its Metabolites by Capillary Electrophoresis

A buffer system of borate with charged (carboxymethyl-β-CD) and uncharged (β-CD) cyclodextrins (CDs) was employed in the chiral resolution and separation of propranolol and its selected major metabolites. By appropriate choice of buffer and additive conditions, chiral resolution of all of the compounds studied was achieved in a single analysis, where near baseline resolution was found for the difficult to resolve propranolol-glycol (Pr-glycol). This has not been observed in previous studies of propranolol and its metabolites.     

离子对色谱法分离氨基醇类对映体

运用离子对色谱法 ,以 (+) 10 樟脑磺酸为手性离子对试剂 ,在二醇柱 (Lichrospher 10 0 DIOL)上 ,分离了苯丙醇胺、美托洛尔、普萘洛尔、肾上腺素和沙丁胺醇 5种氨基醇类对映体。考察了流动相组成和化合物结构对分离选择性的影响。选用的流动相为二氯甲烷 正戊醇 (97 3、V V、内含 2 .2× 10 - 3mol L的樟脑磺酸 ) ,流速为 0 .3mL min。苯丙醇胺、美托洛尔、普萘洛尔、肾上腺素和沙丁胺醇对映体的分离因子分别为 1.2 9、1.2 5、1.2 5、1.33和 1.2 9;它们的分离度分别为 1.5 5、1.78、1.83、1.89和 1.78     

Nonaqueous emulsion polymerization: A practical synthetic route for the production of molecularly imprinted nanospheres

Monodisperse, molecularly imprinted nanospheres were synthesized by nonaqueous (mini)emulsion polymerization using a standard monomer mixture of methacrylic acid and ethylene dimethacrylate containing the drug propranolol as a template. The preparation conditions (solvent, amount of surfactant, and amount of employed template) were extensively varied in order to assess their effect on the properties of the resulting polymer nanoparticles. The molecular recognition capability of the nanospheres was evaluated in batch rebinding experiments, and the effect of the nanosphere preparation conditions as well as of the reaction conditions was investigated. In this way, optimal preparation protocols for molecularly imprinted nanoparticles under nonaqueous conditions with the use of a nonionic emulsifier were identified, which lead to nanospheres with a diameter of around 100 nm having an enhanced capacity of specific template rebinding compared to both nonimprinted nanospheres and to particles obtained by emulsion polymerization in water. Best results were obtained with nanospheres prepared in N,N‐dimethylformamide/n‐hexane with a high functional monomer to template ratio. The enantioselectivity of the rebinding process was also demonstrated. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013