Page 15 - Shimadzu Journal vol.5 Issue1

Posters from These articles were selected by Shimadzu. Relating to clinical research, they derive from posters
Recent presented at ASMS 2017, held June 4-8 in Indianapolis, IN. They feature Shimadzu's state-of-the-art mass
Conferences spectrometry lineup and include cutting-edge technologies.

Selection 1 Clinical research
LC-MS/MS quantitative method development of Herceptin based on selective hydrolysis (nSMOL)
technology and Skyline software
Herceptin is approved for the treatment of early-stage breast cancer that is Human Epidermal growth factor Receptor 2-positive
(HER2+) and has spread into the lymph nodes, or is HER2-positive and has not spread into the lymph nodes. With the wide use of
Herceptin in clinic, the requirement is increasing for precision and accuracy in quantitative analysis of Herceptin in human plasma. With
the development of high performance liquid phase, mass spectrometry and separation technology in biological samples, LC-MS/MS
technology has been used for protein quantity study. Relative to conventional analytical technology ELISA, LC-MS/MS quantitative
method improved the precision and accuracy of protein analysis. For the close combination of protein quantitative technology and
drug development, Shimadzu combined LC-MS/MS analysis platform and proteomics software "Skyline". And we also developed
nSMOL pretreatment technology for selective enzymolysis of Fab zone in monoclonal antibody. Thus, LC-MS/MS combining with
Skyline software and nSMOL technology can provide useful tool for the accurate quantity of monoclonal antibody drugs.

Selection 2 Clinical research
Highly sensitive quantitative analysis of Budesonide from plasma using LC/MS/MS
Budesonide is a glucocorticoid used in the management of asthma, treatment of various skin disorders, and allergic rhinitis.
Budesonide is provided as a mixture of two epimers (22R and 22S). Interestingly, the 22R form is two times more active than the
22S epimer. The two forms do not interconvert.
Inflammation is an important component in the pathogenesis of asthma. Corticosteroids like budesonide have been shown to have
a wide range of inhibitory activities against multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and
lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic and
non-allergic-mediated inflammation. These anti-inflammatory actions of budesonide contribute to their efficacy in the
aforementioned diseases. Budesonide undergoes significant first-pass elimination and its bioavailability is 10 %, which demands its
low-level quantitation in plasma for bioanalysis. Budesonide is formulated as an extended release tablet and inhalers.
Here, an LC/MS/MS method has been developed for highly sensitive quantitation of budesonide from plasma using LCMS-8060, a
triple quadrupole mass spectrometer from Shimadzu Corporation, Japan.

Selection 3 Clinical research
Highly sensitive simultaneous quantitative analysis of estrone and equilin from plasma using
LC/MS/MS
Equilin is an estrogenic steroid produced by horses. It has a total of four double bonds in the A- and B-ring. High concentration of
equilin is found in the urine of pregnant mares. Equilin is one of the estrogens present in the mixture of estrogens isolated from
horse urine and marketed as Premarin. Premarin became the most commonly used form of estrogen for hormone replacement
therapy in the United States of America. Estrone is the major estrogen in Premarin (about 50%) and equilin is present as about
25% of the total. Estrone is a major estrogen that is normally found in women. Equilin is not normally present in women, so there
has been interest in the effects of equilin on the human body.
Here, an LC/MS/MS method has been developed for highly sensitive simultaneous quantitation of estrone and equilin (structure
shown in Figure 1) from charcoal stripped plasma using LCMS-8060, a triple quadrupole mass spectrometer from Shimadzu
Corporation, Japan.

Selection 4 Clinical research
MRM-based validation assay for serum proteomic alterations in meningioma patients
Meningiomas are tumors that arise from the outer layering of the brain namely the dura, arachnoid and pia mater. These tumors
account for nearly 30% of all primary brain tumors and are majorly treated via surgical resection. WHO classifies meningiomas into
three types namely the benign (MGI), atypical (MGII) and anaplastic (MGIII). Recently there are reports of aggravated recurrence
rates and diagnostic ambiguity within the grades and certain molecular signatures have been ascribed to such manifestation.
However apart from the conventional modalities of treatment there are no molecular markers that can be used for diagnosis and
prognosis of these tumors. In this study we attempt to validate differentially expressed proteins in meningioma patients and assess
its utility in context to meningioma pathobiology.

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