Page 6 - Shimadzu Journal vol.2 Issue2

Drug Metabolism 65

the Shimadzu 8030 system that allowed the samples to be rapidly
the ability to develop an accurate and high throughput assay on
freeze/thaw cycles. Critical to these recent discoveries has been
remained within stability specifications when subjected to five
and from -5˚C to -20˚C. Furthermore, the oxytocin ampoules
analysed once subjected to the test conditions in order to

minimize any degradation during analysis. As the work moves on to study drug delivery, metabolism and disposition mechanisms associated with the route of delivery, Dr McIntosh and her team are hoping to use the ultra-high sensitivity of the new Nexera X2-LCMS-8050 to enable sensitive detection and minimally invasive sampling during their studies. This work, although simple in its approach has been invaluable for clinicians and skilled birth attendants in the maternal and global health fields, and has instilled confidence that the potency and efficacy of the oxytocin solution is maintained when inadvertently frozen. 1. RROLI, G., CUESTA, C., ABALOS, E. & GULMEZOGLU, A. M. 2008. Epidemiolog

above 4˚C (as commonly experienced in resource poor settings). In
optimise formulation strategies that can further enhance stability
conditions. The team has identified several deamidation products
current injectable solution when stored at elevated temperatures
indicating complexes resultant from the formation of dimers and
tri-sulfide linkages between oxytocin molecules. All these factors
degradation products and mechanisms has nevertheless fed into
the simultaneous quantitation of the parent oxytocin compound
that govern oxytocin degradation under varying environmental
the analysis has provided valuable insight into the mechanisms
reduced potency and activity of the drug, in particular, for the
turn, although these degradation mechanisms are thought to
the main development project allowing the Monash team to
formed from oxytocin degradation, in addition to instability
occur mainly in solution, understanding and identifying the
are thought to be the key driving forces that influence the
manufacturing and storage. of the inhaled dry powder product, especially during In addition to the development of an inhaled oxytocin powder formulation, work undertaken by the team has also provided invaluable insights into the use and stability of the current oxytocin solution formulation when inadvertently frozen during transport and storage to remote areas. In a recent letter to the editor published in the prestigious New England Journal of Medicine 2 the Monash team demonstrated that oxytocin ampoules remained stable when stored for up to seven days on ice, dry ice If you want to know further information about her research, please visit: http://www.monash.edu.a

injectable solution. Understanding the heat stability of the powder
reliable determination of oxytocin content in the prepared powder
of the oxytocin was degraded after only 2 months under the same
was in contrast to the injectable solution where greater than 20%
with a stability profile that significantly improves upon the current
binary pump LC, incorporating LC-20AD gradient pumps, SIL-20A
development of an inhaled, low cost and needle-free formulation
formulations after storage at 50 °C for up to three months. This
Shimadzu system, Dr. McIntosh’s team was able to demonstrate
Liquid Chromatography (HPLC) system employing a Prominence
formulations. To this end, a robust and highly specific assay for
violet detection system which was validated with high accuracy
associated with oxytocin use in resource poor settings with the
HT autosampler, DGU-20A mobile phase degasser and an ultra
and precision. At this stage, several stability studies have been
formulation has therefore been a significant milestone for the
conducted to determine the amount of drug remaining in the
oxytocin was developed using a Shimadzu High Performance
refrigeration is critical to the success of the product. Such an
inhaled product for the project has been the requirement for
injectable solution after Using the method developed on the
the enhanced stability of the prototype oxytocin dry powder
developed dry powder formulations when compared to the
Crucial to the ongoing development and assessment of the
These promising results have been pivotal in advancing the
innovation has the potential to address current shortfalls
project where the need to eliminate the requirement for
irritation or inflammation within the respiratory tract.
million lives over the next decade. potential to prevent 41 million cases of PPH and save at least 1.4 Parallel to the development of a heat stable dry powder formulation of oxytocin the Monash team has also focused on gaining a fundamental understanding on the mechanisms that govern oxytocin degradation. To this end, a Shimadzu 8030 triple-quadrupole mass spectrometer coupled to a LC-30AD/SIL-30AC UHPLC system has been an invaluable tool in allowing the project to investigate oxytocin stability in greater The sensitivity and ease-of-use of the Shimadzu 8030 system has allowed the Monash team to ro
-Saving lives of mothers after childbirths in the third world-
conditions. depth.

Drug Metabolism The Oxytocin Revolution A global innovation that has the potential to prevent women in developing countries from the fatal loss of blood after childbirth has seen Dr Michelle McIntosh of the Monash Institute of Pharmaceutical Sciences win The Australian Innovation Challenge and a $30,000 prize. The work has drawn favorable reviews around the world and captured the social values that underpin Shimadzu’s Corporate Philosophy. In this article, Dr Michelle McIntosh and her team describe their efforts to make a significant contribution to Global Health. Postpartum haemorrhage (PPH) is the loss of blood (>500 mL) following childbirth that, in the absence of preventive measures, may occur in up to