MSACL 2016 US Abstract

Rapid Determination of Drug Protein Binding Affinity Using Solid Phase Micro Extraction

Craig Aurand (Presenter)
MilliporeSigma

Bio: Craig Aurand is the Technology Program Manager at MilliporeSigma, providing oversight and development of innovative chromatographic and sample preparation techniques. Craig’s primary role is in support of technology development for small molecules analysis, along with development for sample preparation technologies with an emphasis in mass spectrometry. He is responsible for the development of sample preparation devices for bioanalytical applications at Supelco, with numerous presentations and publications focusing on novel chromatographic separations and sample preparation techniques. His most recent research has focused on the field of micro sampling techniques in bioanalysis.

Authorship: Candace Price, David Bell, Emily Barrey
MilliporeSigma, Bellefonte Pa

Short Abstract

In this study, a novel BioSPME micro extraction device is evaluated as a rapid means of determining drug protein binding affinities from plasma. Here, a model set of drugs with varied range of protein binding affinities were utilized to evaluate the utility of the BioSPME sampling technique. Initial studies demonstrate that drug binding affinities can be determined in less than 30 minutes using the micro extraction technique.

Long Abstract

Determination of free circulating drug is important in establishing the pharmacokinetic activity. In most cases, drug-protein complexes are formed thus affecting the active level of circulating drugs. Techniques used for determining drug protein binding levels consist of ultrafiltration, ultracentrifugation and micro dialysis. Automation can be used in the case of micro dialysis, but processing may be greater than 6 hours for equilibrium to be reached. In this study, a novel BioSPME micro extraction device is evaluated as a rapid means of determining drug protein binding affinities from plasma. Here, a model set of drugs with varied range of protein binding affinities were utilized to evaluate the utility of the BioSPME sampling technique. Initial studies demonstrate that drug binding affinities can be determined in less than 30 minutes using the micro extraction technique.

Protein binding affinities for compounds propranolol, warfarin and diclofenac are performed by comparative BioSPME extraction from plasma and phosphate buffered saline. Plasma and buffer samples are plated into 96well plates and extracted by immersion of the BioSPME fibers. The BioSPME fibers are then directly desorbed into solvent direct LC/MS quantitation. Correlation between BioSPME sampling technique and published micro dialysis data has demonstrated to be within 1%.

Preliminary data has demonstrated this as a rapid techinique for determining drug protein binding affinities. Additional studies to evaluate broader protein binding affinity drugs are being conducted.


References & Acknowledgements:


Financial Disclosure

DescriptionY/NSource
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SalaryyesMilliporeSigma
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IP Royalty: no

Planning to mention or discuss specific products or technology of the company(ies) listed above:

yes