The modern pharmaceutical industry appreciates the importance of chirality. Most drugs in the market today, as well as racemic drugs marketed in the earlier years, are chiral compounds. The human body is selective when it comes to chiral drugs, and it interacts differently with racemic drugs (as illustrated in Fig. 1). The human body has receptors for drugs and enantiomers of chiral molecules (contained in the drugs) interact differently with the receptors. As a result, it is possible for one isomer to produce therapeutic activity while the other could be inactive or could produce undesirable effect. Therefore, it is imperative for pharmacists to understand the isomers that can cause unwanted effects to the body. This, in turn, would offer the best opportunity to provide optimal treatment to patients with the appropriate therapeutic control.
Significance of the various methods of chiral separations
Chiral separation is crucial today because one of the enantiomers of a chiral drug maybe active while the other is toxic to the body (as illustrated in Fig.1). Chiral separation is also crucial because regulatory authorities require each enantiomer to be evaluated when developing stereoisomeric drugs.
Why chiral separation techniques are becoming increasingly prominent
During the 1980s, chiral separation was a laborious task. With the advanced technology and knowledge, today, it is easier to separate chiral drugs through enantioseparation. The demand for enantiometrically pure drugs before therapeutic evaluation has also brought about the need to carry out chiral separation. The use of single enantiomers has surpassed the achirals and racemic drugs in the last few years.
Methodologies used to demonstrate a pharmaceutical agent is chiral and how they are developed
There are various means used to determine whether a pharmaceutical agent is chiral or not. One of the means used to detect chirality is through polarimetry. Chiral objects are optically active; they have the capacity to rotate plane polarized light. This involves setting up a light source whose light passes through a polarizer and a sample containing organic molecules. An observer at the end determines the amount of rotation. However, racemates show 00 rotation since they have equal and opposite specific rotations. If a substance is suspected to be chiral but does not show optical activity, then Louis Pasteur’s method of 1860 would come in handy. The racemic mixture is first crystalized, and if the solution under investigation is chiral, then the crystals produced would be mirror images of one another (as illustrated in Fig.2).
Various approaches for obtaining pure enantiomers
The demand for enantiometrically pure agents is gaining prevalence today. To obtain an enantiometrically pure drug, it is necessary to isolate the natural products from the chiral pool. Chiral chromatography is one of the means of obtaining enantiometrically pure agents. It involves passing the racemic mixture through a column packed with Chiral Stationery Phase (CSP). CSP interacts with the enantiomers differently, causing them to elute at different times. The less stable enantiomer elutes first while the more stable enantiomer elutes later. This is based on the premise that enantiomers have varying degrees of affinity for the CSP. There are various approaches to chiral chromatography such as the gas chromatography, High Performance Liquid Chromatography (HPLC) and electrophoresis. HPLC is the most common and is based on the premise that enantioseparation occurs due to differences in energy between the complexes formed by the solute-CSP interactions.
Fractional crystallization is another means of obtaining pure enantiomers. The enantiomers are first crystalized to form diastereomers, and the diastereomers are then separated through a base or an acid to get a pure enantiomer.
Bibliography
Habtemariam, S. (2012). Chirality and chiral chromatography .
