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Drug Metabolism and Bioanalysis Letters

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ISSN (Print): 2949-6810
ISSN (Online): 2949-6829

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Research Article

A Simplified Method for Determining Blood-to-Plasma Ratios in vitro and ex vivo by Matrix Matching with Blank Blood or Plasma

Author(s): Xiaomei Zhang, Gary J. Jenkins, Kelly E. Desino, Jinrong Liu, Mary Larsen and David M. Stresser*

Volume 16, Issue 2, 2023

Published on: 08 September, 2023

Page: [113 - 120] Pages: 8

DOI: 10.2174/2949681016666230817150551

Price: $65

Abstract

Objective: This work describes a simplified, 96-well plate method for determining the blood-to-plasma concentration ratio (BP ratio) for small molecules.

Methods: The need for calibration curves was eliminated using a matrix-matching approach in which blood samples were mixed with blank plasma and plasma samples were mixed with blank blood. As a result, both blood- and plasma-origin samples shared an equivalent matrix ahead of bioanalysis. In the in vitro assay, identical sample matrices were achieved by using the same source of blank plasma and blood.

Results: In humans, a good correlation (R2 = 0.84) was observed between the data obtained in this matrix-matching method and literature values for 11 commercial compounds possessing a wide range of logD values across multiple chemical classes. In addition, this method showed good agreement with in vitro BP ratios for 10 proprietary compounds determined radiometrically (R2 = 0.72) in human and preclinical species. Finally, the in vitro matrix matching method compared favorably to BP ratios determined ex vivo for 13 proprietary and literature compounds (R2 = 0.87) in rat.

Conclusion: This method, suitable for in vitro and ex vivo BP ratio determinations, is operationally efficient, robust, and a useful improvement upon previously published methods.

Keywords: Blood-to-plasma ratio, blood cell partitioning, pharmacokinetics, blood distribution, bioanalysis, radiometrically, blank plasma.

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