Enantioselectivity membranes

The first successful chiral resolutions through enantioselective membranes have been published recently, but few cases are applicable to the preparative scale, mainly due to mechanical and technical limitations. Low flow rates, saturation of the chiral selectors and loss of enantioselectivity with time are some of the common problems encountered and that should be solved in the near future. 

For the separation of racemic mixtures, two basic types of membrane processes can be distinguished a direct separation using an enantioselective membrane, or separation in which a nonselective membrane assists an enantioselective process [5]. The most direct method is to apply enantioselective membranes, thus allowing selective transport of one of the enantiomers of a racemic mixture. These membranes can either be a dense polymer or a liquid. In the latter case, the membrane liquid can be chiral, or may contain a chiral additive (carrier). Nonselective membranes can also... 

Two EPMEs were proposed for the assay of R-baclofen. The electrodes were designed using macrocyclic glycopeptide antibiotic, teicoplanin [45]. Acetonitrile was added to the teicoplanin to design a modified teicoplanin-based electrode. The linear concentration ranges for the proposed enantioselective, membrane electrodes were 10 7-10 4mol/L for teicoplanin-based electrode and 10 6-10 4mol/L for the electrode based on teicoplanin modified with acetonitrile. The slopes of the electrodes were 60.0 and 57.2 mV/pR-baclofen for teicoplanin and teicoplanin modified with acetonitrile-based electrodes, respectively. The enantioselectivity was determined over S-baclofen. The proposed electrodes can be employed reliably for the assay of R-baclofen raw material and from its pharmaceutical formulation, Norton-Baclofen tablets. 

Three EPMEs based on macrocyclic glycopeptide antibiotics— vancomycin and teicoplanin (modified or not with acetonitrile)—were proposed for the determination of l- and D-enantiomers of methotrexate (Mtx) [48]. The linear concentration ranges for the proposed enantioselective membrane electrodes were between 10 6 and 10-3 mol/L for l- and D-Mtx. The slopes of the electrodes were 58.00 mV/pL-Mtx for vancomycin-based electrode, 57.60 mV/pD-Mtx for teicoplanin-based electrode and 55.40 mV/pD-Mtx for teicoplanin modified with acetonitrile-based electrode. The detection limits of the proposed electrodes were of 10 8 mol/L magnitude order. All proposed electrodes proved to be successful for the determination of the enantiopurity of Mtx as raw material and of its pharmaceutical formulations (tablets and injections). 

An EPME based on vancomycin was proposed for the assay of D-pipecolic acid [50]. The linear concentration range for the proposed enantioselective membrane electrode is 10 9-10 6mol/L with the slope of electrode function 60.2 mV/p(D-pipecolic acid). The enantioselectivity was determined over L-pipecolic acid. The proposed electrode could be reliably employed for the assay of D-pipecolic acid in serum samples. 

Progress in better understanding of fouling phenomena and their prevention, improving of membrane selectivity, and development of new enantioselective membranes, are some examples of sectors where basic research can contribute. 

Specificity is a property of monocomponent systems and it occurs when the method is free of interference. Selectivity is related to the complexity of the matrix and it occurs when not more than one ion (molecule) interferes in determination. Enantioselectivity is a relatively new term introduced for the assay of enantiomers.257258 An analytical method is enantioselective when it can discriminate between enantiomers. Enantiospecificity is an extreme case of enantioselectivity. It is possible to create the conditions for a highly enantioselective analysis, and in this case enantiospecificity can also occur. For example, a maltodextrin with dextrose equivalence (DE) of 4.0 to 7.0 was used in capillary zone electrophoresis as a stationary phase for the separation of the enantiomers,259 and also in the design of a potentiometric, enantioselective membrane electrode.260 The method for capillary zone electrophoresis is enantioselective, as it is for the potentiometric method. 

The most sensitive enantioselective separation technique is capillary zone electrophoresis. Here, the detectors utilized are not sensitive enough to be able to detect the enantiomers. In the case of sensors, amperometric biosensors have been found to be most sensitive.264 A better enantioselectivity was found for potentiometric, enantioselective membrane electrodes because a direct interaction between the chiral selector and enantiomer occurred.282 285... 

Immunoreactions have proved to exhibit good enantioselectivity. They can yield both a sensitivity higher these biosensors and an enantioselectivity higher than potentiometric, enantioselective membrane electrodes. 

Since in most cases only one enantiomer possesses a desired pharmacological activity, it is necessary to construct enantioselective sensors to improve the quality of analysis due to the high uncertainty obtained in chiral separation by chromatographic techniques.315 For this purpose, enantioselective amperometric biosensors and potentiometric, enantioselective membrane electrodes have been proposed.264 The selection of one sensor from among the electrochemical sensor categories for clinical analysis depends on the complexity of the matrix because the complexity of different biological fluids is not the same. For example, for the determination of T3 and T4 thyroid hormones an amperometric biosensor and two immunosensors have been proposed. The immu-nosensors are more suitable (uncertainty has the minimum value) for direct determination of T3 and T4 thyroid hormones in thyroid than are amperometric biosensors. For the analysis of the same hormones in pharmaceutical products, the uncertainty values are comparable. 

This chapter provides a discussion on the skin s stereoselective permeation, metabolism, and binding of different stereoforms and racemates of chiral molecules. Not only is the published information in this field limited but also there are some controversial data that have been reported. Additional studies are required to answer the following questions Is the skin an enantioselective membrane Can this characteristic be confirmed by in vitro and in vivo experiments Since wide differences exist between the laboratory models with regard to their biochemical composition and permeability, how can these issues be addressed in the preclinical investigations involving... 

A potentiometric enantioselective membrane electrode with bonded 2-hydroxy-3-trimethyl-ammoniopropyl-/3-CD has been used for the enantio-purity determination of several L-enantiomers. The /3-CD-ferrocene inclusion complex has been used for the amperometric determination of ascorbic acid. Alkylated a-, P- and y-CDs have been incorporated in an ion-selective electrode as neutral ionophores and this electrode was used for the potentiometric andamperometric determination of the tricyclic antidepressives and their hydrochloride salts [80]. Cyclic voltammetry was used for measuring the association constants of inclusion complexes. 

---