Abstract
Plasma protein binding is an important determinant of the pharmacokinetic properties of chemical compounds in living organisms. The aim of the present study was to determine the index of protein binding affinity based on chromatographic experiments. The question is which chromatographic environment will best mimic the drug–protein binding conditions. Retention data from normal phase thin-layer liquid chromatography (NP TLC), reversed phase (RP) TLC and HPLC chromatography experiments with 129 active pharmaceutical ingredients (APIs) were collected. The stationary phase of the TLC plates was modified with protein and the HPLC column was filled with immobilized human serum albumin. In both chromatographic methods, the mobile phase was based on a buffer with a pH of 7.4 to mimic physiological conditions. Chemometric analyses were performed to compare multiple linear regression models (MLRs) with retention data, using protein binding values as the dependent variable. In the course of the analysis, APIs were divided into acidic, basic and neutral groups, and separate models were created for each group. The MLR models had a coefficient of determination between 0.73 and 0.91, with the highest values from NP TLC data.
Highlights
The introduction of all unrelated variables into the multiple linear regression (MLR) analysis did not increase the correlation with the PBabn (R = 0.57, nabn = 129)
Analysis of the HPLCHSA data showed that the creation of an independent very slightly for groups of different sizes, with R values within 0.56–0.63 for the number chromatographic variable containing a Protein binding (PB) value did not directly increase the correlation with the dependent variable PB in any group of cases
Such analytical models for the investigation of drug–protein binding in the body can be based on simple laboratory analyses such as TLC or HPLC
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Protein binding (PB) is an important consideration in the design of new drug substances. The free form of the drug is capable of pharmacodynamic action and passing through biological barriers. As proteins are widely distributed throughout the human body, it seems impossible to prevent them from interacting with medications [1,2]
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