The chemistry behind every medicine that goes to market has a significant impact on how it is made. Not only does an in-depth understanding of molecular makeup provide information about how a drug can react within the body, but it also
supports quality control to ensure that the drug is exactly what it
is supposed to be.
All medicine requires quality analysis, whether new to the
clinic or a time-tested treatment. Along with confirmation of the
(obvious) regulated amount of active ingredient, inclusion of prod-uct-based related compounds and process-based impurities can
cause issue with overall drug efficacy, safety and stability. Unwanted impurities that could arise throughout the drug development
lifecycle are a key concern across formulation and manufacturing,
pushing companies to follow regulatory guidelines and constantly
improve upon current analytical methods so that only safe and
effective drugs go to market.
When investigating pharmaceuticals, such as those involved in
the treatment of cancer, quality and attention to side effects can direct drug analysis. Cancer treatments in particular are wide-ranging and generated in many forms, from traditional chemotherapies
to innovative immunotherapies that are targeted to a specific
cancer type. As one of the most researched disease classes, cancer
and cancer therapies are a potent example of the importance of
progressing drug quality analysis to encompass different types of
drugs that can result in finding unknown impurities.
Cancer is the second leading cause of death, with one in six
deaths contributed to the disease, worldwide. Projected estimates
of cancer incidence suggest that the number of new cases is expected to rise by approximately 70 percent over the next two decades.
Given the unfortunate increase in cancer prevalence across the
world, substantial energy in the cancer community is focused on
improving older treatments and investigating novel therapies.
Quality and purity monitoring in the final drug formulation of
both old and new cancer treatments is of the utmost importance.
Questions must be asked regarding whether any additional sub-
stances affect the drug’s activity or increase potential negative side
effects. Evaluating the chemistry behind each treatment is a key
part of the process that allows pharmaceutical companies to be
sure that a drug is effective and safe.
There’s something about impurities
Typical methods applied to cancer drug quality assessment, including ultra-high performance liquid chromatography (UHPLC)
combined with ultraviolet and visible (UV/Vis) detection, aim
to provide an overall view of drug components while still being
specific and sensitive enough to detect low abundance impurities.
While UV/Vis detection can easily identify some impurities and
other compounds present in a sample, challenges arise with selec-
tivity and identification of impurities that do not have inherent
chromophores or vary in response factors (such as extinction
coefficients). These cases bring a level of uncertainty to impurity
analysis that cannot be tolerated when quality checking a drug.
In addition to ensuring accurate identification of impurities,
testing and monitoring approaches must also conform to the
International Council for Harmonisation of Technical Require-
Combination of Techniques
Proves More Effective
in Drug Testing
While single methods have their own unique challenges,
combining and supplementing with complementary approaches
can ensure a more complete analysis.
by Michael Menz, Frank Steiner and Ian Acworth, Thermo Fisher Scientific, Inc.
The chemical structure of paclitaxel, a cancer chemotherapy drug. Atoms
are represented as spheres with conventional color coding: hydrogen (white),
carbon (grey), nitrogen (blue), oxygen (red).