The pharma industry is moving towards the development of new pharmaceutical products containing single entantiomers of chiral molecule as active ingredients. WPF speaks to Rina K. Dukor, President and CEO of BioTools, about the use of spectroscopic instruments in chiral analysis.

Generally speaking, spectroscopy helps to speed up the analysis of all kinds of molecules. At present, there are many spectroscopic techniques that give scientists information about the structure and environment of the molecules in question. This assists the companies in getting a better understanding of the processes involved in manufacturing pharmaceuticals, such as blending and drying and in turn decreases failures and helps get the product to market faster.

‘There are a lot of spectroscopic techniques out there, especially in the area of vibrational spectroscopy’, says Rina Dukor, CEO of BioTools. ‘But we think the market is missing an instrument, not for looking at general aspects of pharmaceuticals as most instruments do, but for specific properties, such as chirality.’

After all, the key biological molecules in nature are chiral. Therefore, BioTools has focused on developing spectroscopic instrumentation for chiral analysis. Currently, it is possible to quickly gain general information about drugs – for example, the right concentration of the API. ‘However, so far, there has been no way of telling on-line whether a molecular sample has the optimum percentage of chirality’, Dukor explains. ‘That is why our company is developing a technique for fast determination of a property known as enantiomeric excess.’

How it works

‘The actual technique was developed 30 years ago, in 1974, but was never used commercialized,’ says Dukor. Technology had to advance to be able to measure these small signals reliably. Dukor describes the technique in basic terms: ‘Take IR unpolarised light, then polarise it into left and right circularly polarised states. Let that light, modulating between left and right states, interact with the chiral molecule, and the difference in intensity that you get is the same, but opposite in sign for opposite enantiomers.’

The principle can be compared with one’s left and right hands and a glove: the left hand will not fit perfectly with the right glove the way the right hand does . When used in the infrared region of the spectrum, the technique is called vibrational circular dichroism (VCD) and its use helps companies find out which enantiomer of a chiral molecule they have: the left- or the right-handed form.

Key markets

This development, predominantly, targets pharmaceutical companies working with chiral drugs. There are two main applications BioTools is aiming for:

  • The determination of absolute configuration
  • The determination of percent enantiomeric excess (%EE)

The determination of absolute configuration tells scientists which chiral molecule they have. The gold standard now is to grow a single crystal and use X-ray diffraction. This process, however, is expensive and takes a long time – sometimes months or never if the sample is an oil. VCD offers an unambiguous determination of absolute configuration of chiral molecules in solution. It is fast, easy and affordable.

The second market application evolves around the company’s future vision. During manufacturing of chiral molecules, there are many parameters in the reactor that affect chirality, such as temperature, pressure and so on. Thus there is a need to monitor changes in %EE on-line or at-line. Current chromatographic methods can be very time-consuming and expensive. BioTools has developed a unique method for obtaining the %EE. By putting the instrument close to the reactor, one can measure the chirality in real time and thus, obtain %EE without disrupting the process of making the molecule. ‘This has never been done before,’ Dukor stresses. ‘It will not only save companies time and money, but prevent them from having to stop the process, or remove a sample, just to make necessary measurements.’ Once the continuous measurement of the %EE has been setup, the process can be continued until the desired balance between degree of product synthesis and %EE has been achieved.

Timely stance

The prototype issue of this technique is already being worked on, looking at reactions of chiral molecules on-line, in real time in their reacting environment on a small scale. ‘We are planning to offer this system on- and off-line by 2006,’ says Dukor.

Although a small company, BioTools has already made a name for itself among the big pharmaceutical companies with its VCD spectrometer and has a successful future ahead in several niche markets.