OPTICAL ROTATION
Carbon is the core element around which the chemistry of lifehas evolved. Early chemists observed many instances of pairs of
organic compounds that have identical physical properties (exactly
the same energy, solubility, boiling and melting points, NMR and IR
spectra, etc.). However, these pairs or compounds were considered
as “optically active” since they were observed to rotate a beam of
polarized light in equal amounts, but different directions.
As the impact of chirality in the drug industry continues to grow,
technologies to produce single enantiomer molecules are increasingly important not only to the clinical success of the drug but also
to its commercial success as complex single enantiomer drugs are
often very expensive to manufacture. Specifications for the final
product need to assure identity, strength, quality and purity from the
stereochemical perspective.
Organic molecules result from carbon bonding with four other moecules in a tetrahedral arrangement. Stereoisomers are molecules
that have the same molecular formula and the same connectivity
of atoms, but differ only in the three-dimensional arrangement of
those atoms in space. A chiral molecule is non-superimposable
R. D. Laboratories, Inc. is ready to assist you in ensuring the quality
of your optically active pharmaceuticals and ingredients. We use
polarimetery to evaluate the identity, purity and freedom from contamination by optical antipodes optically active materials.
on its mirror image, so that the mirror image is actually a different
molecule.
The magnitude of the optical rotation is affected by the concentration of the solution, the length of the path of light, the wavelength
of light and the temperature. The specific rotation [α] is defined as
the observed angle of optical rotation when plane-polarized light is
passed through a sample with a path length of 1 dm and a sample
concentration of 1 g/mL. The specific rotation of a pure material
is an intrinsic property of that material at a given wavelength and
temperature.
Many biologically active molecules, including amino acids (the
building blocks of proteins), and sugars are chiral. In biological
systems, most of these compounds are of the same chirality. All
naturally-occurring amino acids exist as only one of the two possible enantiomers, and so by extension, all proteins and enzymes
are also chiral.
The common way to refer to the chirality of a molecule is based on
the direction that it rotates a plane of light. The clockwise direction
is termed dextorotary (d, or “+”) and the counterclockwise direction
is levorotary (l or “-” ). The modern descriptors R and S or α and β do
not define optical rotation but rather the orientation of bonding to a
chiral atom. Many “man made” compounds, including active pharmaceutical ingredients, have chiral centers and may be composed
of enantiomeric pairs or racemates often designated by ± or RS and
have opposing rotation and no optical activity.
Drug regulatory authorities are paying particular attention to the
potentially different pharmacological and toxicological profiles of
enantiomers. The U.S. Food and Drug Administration (FDA) issued
a policy regarding the development of new stereoisomeric drugs in
1992. Although the FDA leaves the decision to pursue a racemic or a
single-enantiomer formulation of a new drug to its developers, it will
likely be more difficult to obtain approval for racemates. The industry as a whole is interested in developing more potent, selective and
specific drugs. In the last 10 years, approximately 80% of the smallmolecule drugs approved by the FDA were chiral of which nearly 75%
were approved as single enantiomer products.
R.D. Laboratories, Inc. utilizes a Rudolph Research Analytical Autopol V with six wavelengths (325nm, 365nm, 405nm, 436nm, 546nm
and 589nm) and precise temperature control from 15°C to 30°C
allows us to measure 99% of all optical rotation monographs found
in the USP, EP, JP and BP. Non compendia determinations can be
performed as well.
The Autopol V is one of the most accurate and precise
digital polarimeters available with a resolution of
0.001º and reproducibility of 0.002º arc optical
rotation. The polarimeter has been fully
validated (IQ/OQ/PQ) using NIST traceable
calibration standards.