Dataset Information

Characterization of plasma protein binding dissociation with online SPE-HPLC.

ABSTRACT: A novel parameter of relative recovery (R re) was defined and determined by online SPE-HPLC to characterize plasma protein binding (PPB) kinetics of highly plasma binding drugs. The proportional relationship of R re with k off of PPB has been established with a new SPE model. A rapid, easy to use method could potentially be used to categorize PK properties of the drug candidates in the decision process of drug discovery and development.

SUBMITTER: Li P

PROVIDER: S-EPMC4602217 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Characterization of plasma protein binding dissociation with online SPE-HPLC.

Li Ping P Fan Yiran Y Wang Yunlong Y Lu Yaxin Y Yin Zheng Z

Scientific reports 20151013

A novel parameter of relative recovery (R re) was defined and determined by online SPE-HPLC to characterize plasma protein binding (PPB) kinetics of highly plasma binding drugs. The proportional relationship of R re with k off of PPB has been established with a new SPE model. A rapid, easy to use method could potentially be used to categorize PK properties of the drug candidates in the decision process of drug discovery and development. ...[more]

PMID: 26460813

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Project description:Commercial preparations of Ginkgo biloba are very complex mixtures prepared from raw leaf extracts by a series of extraction and prepurification steps. The pharmacological activity is attributed to a number of flavonoid glycosides and unique terpene trilactones (TTLs), with largely uncharacterized pharmacological profiles on targets involved in neurological disorders. It is therefore important to complement existing targeted analytical methods for analysis of Ginkgo biloba preparations with alternative technology platforms for their comprehensive and global characterization. In this work, (1)H NMR-based metabolomics and hyphenation of high-performance liquid chromatography, photo-diode array detection, mass spectrometry, solid-phase extraction, and nuclear magnetic resonance spectroscopy (HPLC-PDA-MS-SPE-NMR) were used for investigation of 16 commercially available preparations of Ginkgo biloba. The standardized extracts originated from Denmark, Italy, Sweden, and United Kingdom, and the results show that (1)H NMR spectra allow simultaneous assessment of the content as well as identity of flavonoid glycosides and TTLs based on a very simple sample-preparation procedure consisting of extraction, evaporation and reconstitution in acetone-d(6). Unexpected or unwanted extract constituents were also easily identified in the (1)H NMR spectra, which contrasts traditional methods that depend on UV absorption or MS ionizability and usually require availability of reference standards. Automated integration of (1)H NMR spectral segments (buckets or bins of 0.02 ppm width) provides relative distribution plots of TTLs based on their H-12 resonances. The present study shows that (1)H NMR-based metabolomics is an attractive method for non-selective and comprehensive analysis of Ginkgo extracts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-009-0195-x) contains supplementary material, which is available to authorized users.

Dataset Information

Characterization of plasma protein binding dissociation with online SPE-HPLC.

Publications

Characterization of plasma protein binding dissociation with online SPE-HPLC.

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