Enantiomers drugs

The first partial chiral resolution reported in CCC dates from 1982 [120], The separation of the two enantiomers of norephedrine was partially achieved, in almost 4 days, using (R,R )-di-5-ric my I tartrate as a chiral selector in the organic stationary phase. In 1984, the complete resolution of d,1-isoleucine was described, with N-dodecyl-L-proline as a selector in a two-phase buffered n-butanol/water system containing a copper (II) salt, in approximately 2 days [121], A few partial resolutions of amino acids and drug enantiomers with proteic selectors were also published [122, 123],... 

Edholm, L.E., Lindberg, C., Paulson, J. (1988). Determination of drug enantiomers in biological samples by coupled column liquid chromatography and liquid chromatogra-phy-mass spectrometry. J. Chromatogr. 424, 61-72. 

Sandra, P, Kot, A., David, F. (1994). Subcritical fluid chromatography of coupled CSP columns for the separation of drug enantiomers. Chim. Oggi. 12, 33-36. 

Walhagen, A., Edholm, L.E. (1989). Coupled-column chromatography on immobilized protein phases for direct separation and determination of drug enantiomers in plasma. J. Chromatogr. 473, 371-379. 

Francotte, E.R. Enantioselective Chromatography for the Preparation of Drug Enantiomers, ISCD-15, Shizuoka, Japan, October 2003. 

CE has been established as a very efficient technique for the separation of drug enantiomers. Chiral separations in CE are also based on the formation of diastereomeric complexes between the enantiomers and a chiral selector. The main advantages of the technique are its high efficiency, short analysis times, versatility due to the great variety of chiral selectors that can be added to the BGE, short equilibration times required when changing the chiral selector and low consumption of selector. °... 

There are also known cases of drug enantiomers that possess completely different therapeutic properties. The (+)-2/ ,35 -stereoisomer of propoxyphene (dextropropoxyphene) is marketed as an analgesic agent, whereas its enantiomer ( )-(25, 3/ )-propoxyphene (levopropoxyphene) is available as an effective anti-tussive agent [3]. The enantiomers of some chiral drugs are known to possess essentially identical qualitative and quantitative pharmacological activities, for example, the antihistamine promethazine, which is marketed as a racemate [5]. 

E Szoko, J Gyimesi, L Barcza, K Magyar. Determination of binding constants and the influence of methanol on the separation of drug enantiomers in cyclodextrin-modified capillary electrophoresis. J Chromatogr A 745 181-187,... 

A Amini, D Westerlund. Evaluation of association constants between drug enantiomers and human aracid glycopotein by applying a partial-filling technique in affinity capillary electrophoresis. Anal Chem 70 1425-1430, 1998. 

Table 1 Separation of Drug Enantiomers by CE Using Proteins as Chiral Selectors... 

Y Ding, X Zhu, B Lin. Study of interaction between drug enantiomers and serum albumin by capillary electrophoresis. Electrophoresis 20 1890-1894, 1999. 

J Haginaka, N Kanasugi. Separation of drug enantiomers by capillary zone electrophoresis using ovoglycoprotein as a chiral selector. J Chromatogr A 782 281-288, 1997. 

F Kilar. Stereoselective interaction of drug enantiomers with human serum transferrin in capillary zone electrophoresis. Electrophoresis 17 1950-1953, 1996. 

N Mano, Y Oda, Y Ishihama, H Katayama, N Asakawa. Investigation of interactions between drug enantiomers and flavoprotein as a chiral selector by affinity capillary electrophoresis. J Liq Chromatogr 21 1311-1332, 1998. 

Finally, because enzymes are usually stereoselective, one drug enantiomer is often more susceptible than the other to drug-metabolizing enzymes. As a result, the duration of action of one enantiomer may be quite different from that of the other. Similarly, drug transporters may be stereoselective. 

The Pirkle-type chiral stationary phases are quite stable and exhibit good chiral selectivities to a wide range of solute types. These CSPs are also popular for the separation of many drug enantiomers and for amino acid analysis. Primarily, direct chiral resolution of racemic compounds were achieved on these CSPs. However, in some cases, prederivatization of racemic compounds with achiral reagents is required. The applications of these phases are discussed considering re-acidic, re-basic, and re-acidic-basic types of CSP. These CSPs have also been found effective for the chiral resolution on a preparative scale. Generally, the normal phase mode was used for the chiral resolution on these phases. However, with the development of new and more stable phases, the reversed phase mode became popular. 

Francotte, E. (2001) Enantioselective chromatography as a powerful alternative for the preparation of drug enantiomers. J, Chromatogr. A 906, 379-397. 

C. Vandenbosch, D. Luc Massart, and W. Linder, Evaluation of six chiral stationart phases in LC for selectivity towards drug enantiomers, J. Pharm. Biomed. Anal., 10 895 (1992). 

Apart from being able to distinguish between diastereomers the analytes must also be separated from all other potentially chiral interferences that either are endogenous to the mixture or are likely to be produced in the derivatization reaction. Accordingly interest has been directed towards the separation of drug enantiomers by high performance liquid chromatography (HPLC). The technique can provide a quick, reliable and sensitive method for chiral resolution and for the determination of the enantiomeric purity. 

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