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Understanding performance of 3D-printed sorbent in study of metabolic stability

2020; Elsevier BV; Volume: 1629; Linguagem: Inglês

10.1016/j.chroma.2020.461501

1873-3778

Szymon Ulenberg, Paweł Georgiev, Mariusz Belka, Grzegorz Ślifirski, Martyna Z. Wróbel, Andrzej Chodkowski, Marek Król, Franciszek Herold, Tomasz Bączek,

Crystallization and Solubility Studies

Metabolic stability tests are one of the fundamental steps at the preclinical stages of new drug development. Microsomes, used as a typical enzymatic model of liver biotransformation, can be a challenging matrix for analytical scientists due to a high concentration of cellular proteins and membrane lipids. In the work, we propose a new procedure integrating biotransformation reaction with SPME-like protocol for sample clean-up. It is beneficial to increase the overall quality of results in contrary to the typical protein precipitation approach. A set of ten arylpiperazine analogs, six of which are considered promising drug candidates (and four are accepted drugs) were used as a probe to assess the goodness of the newly proposed approach. In order to promote an efficient extraction protocol, a new, miniaturized shape of a sorbent, suitable to perform the extraction in 100 µL of the sample has been designed. Termination of the biotransformation process by protein denaturation with hot water was additionally evaluated. A quantitative structure-property relationship (QSPR) study using Orthogonal Partial Least Squares (OPLS) technique to reveal insights to the sorption mechanism was also performed. The obtained results showed the new 3D-printed sorbent can be an attractive basis for the new sample preparation approach for metabolic stability studies and an alternative for commercially available protocols based on solid-phase microextraction (SPME) or solid-phase extraction (SPE) principles.