Introduction: Most of the drugs substance single enantiomer is active. In such cases the inactive enantiomer is considered as an impurity, e. g. If Dextro form is active then in this case levo form is considered as an impurity. An enantiomer can be named by the direction in which it rotates the plane of polarized light. An optical isomer can be named by the spatial configuration of its atoms. Clockwise rotation of the light traveling toward the viewer is labelled (+) or R (in Latin Rectus for right) also termed as d-isomer i.e. dextrorotatory enantiomer. Its mirror-image is labelled (−) or S (in Latin Sinister for left) also termed as l-isomer i.e. levorotatory enantiomer. The R / S system is an important nomenclature system for representing enantiomers. This method labels each chiral centre R or S according to a system by which its substituents are each assigned a priority, according to the Cahn–Ingold–Prelog priority rules (CIP), based on atomic number.

1. Overview and Determination of Enantiomeric impurities
Structures of a) ofloxacin (R-form) and b) levofloxacin.

2. Or Include below structure from Veeprho Website Levofloxacin R-Isomer / Dextrofloxacin
Introduction: Most of the drugs substance single enantiomer is active. In such cases the
inactive enantiomer is considered as an impurity, e. g. If Dextro form is active then in this case
levo form is considered as an impurity.
An enantiomer can be named by the direction in which it rotates the plane of polarized light.
An optical isomer can be named by the spatial configuration of its atoms. Clockwise rotation of
the light traveling toward the viewer is labelled (+) or R (in Latin Rectus for right) also
termed as d-isomer i.e. dextrorotatory enantiomer. Its mirror-image is labelled (−) or S (in
Latin Sinister for left) also termed as l-isomer i.e. levorotatory enantiomer.
The R / S system is an important nomenclature system for representing enantiomers. This
method labels each chiral centre R or S according to a system by which its substituents are each
assigned a priority, according to the Cahn–Ingold–Prelog priority rules (CIP), based on atomic
number.
Enantiomeric Impurities
Chiral molecules are normally called enantiomers. Chiral separation plays a very important role
in the modern pharmaceutical analysis. Separation and identification of chiral impurities is very
crucial. As per ICH guidelines, only active enantiomer of the drug has to be marketed, so there
is attention on separation of the inactive enantiomer which acts as a chiral impurity. The
impurities present in the enantiomers having similar chemical structure but different spatial
orientation and pose various toxic adverse effects on bioavailability and efficacy. Hence it is
essential to separate these impurities.
Presently there are more than 50% of the drug substances were chiral compounds. The
enantiomers of chiral drugs can differ in their interactions with enzymes, proteins, receptors,

3. and other chiral molecules, which result in differences in biological activity. The effect on
biological activity can be further extended to variations in pharmacology, pharmacokinetics,
metabolism, and toxicity. The body may metabolize each enantiomer by separate pathways to
generate differing pharmacological activity. Therefore, one isomer may produce the desired
therapeutic effect while another may be inactive or produce adverse effects.
Analytical Methods for Determination of Enantiomeric Impurities:
To ensure that chiral impurities are adequately controlled, suitable analytical methods are
required. Several analytical techniques have been used for the determination of chiral
impurities. Physicochemical methods that can be used to provide information about chiral
drugs are listed below.
A. High-Performance Liquid Chromatography (HPLC)
Chiral HPLC method has recognized to be one of the finest methods for chiral separation,
and quantification of enantiomers of chiral drugs. Chiral HPLC may be used to separate
mixtures of enantiomers directly without forming diastereoisomeric derivatives.
Separations can be achieved through the use of chiral stationary phases, or chiral mobile
phase in combination with achiral columns.
B. Gas Chromatography
Stationary phases altered with chiral agents are available for the separation of enantiomers.
C. Nuclear Magnetic Resonance (NMR)
NMR is a suitable instrument for the determination of enantiomeric composition. This is
achieved by making the NMR signals for the protons of the enantiomers non-equivalent by
the use of chiral lanthanide shift reagents, chiral solvating or derivatizing agents.
D. Capillary electrophoresis (CE)
Capillary electrophoresis is fast method uses cyclodextrins and substituted cyclodextrins as
the most common chiral selectors.
E. Polarimeter
This method can be used to distinguish between enantiomers because they rotate the plane
of polarized light in opposite directions but in equal amounts.
F. X-ray Diffractometer
X-Ray diffractometer in the solid state could be used for the estimation of complete
conformation of molecules and to differentiate conglomerates from racemic compounds.
G. Melting Point
The melting points may be used in characteristic, specific enantiomers from the racemate.

4. Conclusion:
Maximum drug substances are chiral in nature hence it is necessary to develop a suitable
enantiomeric method. Enantiomerically only active enantiomer drug compounds will be one of
the standards for drug substances to be accepted by the US Food and Drug Administration and
as per ICH guideline. Chiral analyses play an important role in the pharmaceutical business and
there is growing requirement for a significant means of chiral analysis for quality control and
detection of trace enantiomeric impurities particularly when it is verified to be toxic.
References:
1. ICH, Q3A(R2) Impurities in New Drug Substances,
2. ICH, Q3B(R2) Impurities in New Drug Products,
3. ICH, Q2(R1) Validation of Analytical Procedures: Text and Methodology,
4. Relationship between physical properties and crystal structures of chiral drug’’ Z.jane
Li and David J.W.Grant,
5. Encyclopedia of pharmaceutical technology,
6. Tsukamoto M, Kagan HB (2002) Recent Advances in the Measurement of
Enantiomeric Excesses,
7. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-
products/applications-submissions/guidance-documents, Guidance for Industry:
Stereochemical Issues in Chiral Drug Development
8. A.J.Romero and C.T.Rhodes, Chirality.