6.4. Polarimetry, ORD and CD Spectroscopy

The pharmacopoeias generally apply the determination of the specific optical rotation for the characterisation of the optical purity of drugs administered as the pure enantiomer. The measurements are prescribed at D-line of sodium (589.3 nm) or rarely at some wavelenghts in the visible region of the mercury lamp (365,405,436, 546, 578 nm) and the value of the specific optical rotation should fall into a range prescribed in the individual monographs. At the shorter wavelengths the values are higher and hence the sensitivity of the measurement can be considerably increased. Generally speaking, however, the sensitivity of the simple polarimetric measurement is low for the estimation of the nonwanted enantiomer as compared with the chromatographic, electrophoretic and NMR methods described in Sections 6.2, 6.3 and 6.5 and due to the possible contribution of other chiral impurities to the measured value the selectivity is also poor. This means that the measurement of the specific optical rotation gives only a rough estimate of the enantiomeric composition. Of the modern chiroptical techniques the measurement of optical rotatory dispersion (ORD) and circular dichroism (CD) presents much more sensitive, selective and accurate methods for the determination of the optical purity. This is usually expressed as the enantiomeric excess (ee) or enantiomeric purity (EP): ee(%) ---100(x* x)/(x* + x), where x* is the mole fraction of the enantiomer in excess. The optical purity (OP) defined as the ratio of the actual specific rotation to the specific rotation of an enantiomerically pure sample is practically the same value. (There is a considerable difference between the terminologies used here and in chiral chromatography and electrophoresis. The ee value for the mixture of 99% of R and 1% of S enantiomer is 98%, i.e. 98% enantiomeric excess + 2% racemate, while in the case of chiral chromatography and electrophoresis the ratio of the areas of the separated peaks of R and S is 99:1.) The above mentioned chiroptical methods applied for the estimation of enantiomeric purity of drugs can be divided into two groups: