In vitro permeability of MDPV across Caco-2 cells for assessment of intestinal absorption and enantioselectivity

Authors

  • A. S. Almeida Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira nº 228, 4050-313 Porto, Portugal; Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR), Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, s/n, 4450-208 Matosinhos, Portugal; UCIBIO—Applied Molecular Biosciences Unit, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira nº 228, 4050-313 Porto, Portugal; Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira nº 228, 4050-313 Porto, Portugal
  • B. Silva UCIBIO—Applied Molecular Biosciences Unit, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira nº 228, 4050-313 Porto, Portugal; Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira nº 228, 4050-313 Porto, Portugal
  • F. Remião UCIBIO—Applied Molecular Biosciences Unit, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira nº 228, 4050-313 Porto, Portugal; Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira nº 228, 4050-313 Porto, Portugal
  • C. Fernandes Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira nº 228, 4050-313 Porto, Portugal; Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR), Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, s/n, 4450-208 Matosinhos, Portugal

DOI:

https://doi.org/10.48797/sl.2023.61

Keywords:

Selected Oral Communication

Abstract

Background: Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone (MDPV), are widely studied chiral psychoactive substances [1]. Enantioselectivity studies on the toxicokinetic of synthetic cathinones are still scarce [2], namely on their ability to cross the intestinal membrane, which was evaluated only for methylone and pentedrone [3]. To isolate enantiomers for these studies, liquid chromatography (LC) using chiral columns has been the technique of choice [4]. Objective: The aims of this work were the semi-preparative enantioresolution of the enantiomers of MDPV and development and validation of an UHPLC-UV method to further evaluate the potential enantioselectivity in intestinal permeability using the Caco-2 cell line. Methods: A semi-preparative LC method using a polysaccharide-based column was optimized to obtain the enantiomers of MDPV. Caco-2 monolayers were exposed to each enantiomer and samples were collected and quantified by UHPLC-UV. For the validation of the UHPLC-UV method, specificity, linearity, accuracy, precision, limit of detection (LOD) and limit of quantification (LOQ) and samples’ stability were evaluated [5]. Results: The enantiomers were successfully separated by the optimized LC method with good resolution (Rs of 1.7) and enantioselectivity (α of 1.4), being collected with high enantiomeric ratios (>95%) and recovery rates (>92%). Regarding the UHPLC-UV, high selectivity and good linearity were obtained (r2 > 0.999). Acceptable accuracy (between 102-109%) and inter-day and intra-day precisions (CV < 15%) low LOD and LOQ values (0.063 μM and 0.19 μM, respectively) were also observed. Samples were stable for 6 weeks of storage in different temperatures (room temperature, 4 °C, -20 °C and -80 °C). Conclusions: The enantiomers of MDPV were found to be highly permeable across the Caco-2 monolayer and enantioselectivity was found for the Papp values in the basolateral (BL) to apical (AP) direction.

References

1. Almeida AS, Silva B, Silva JP, Pereira JA, Remião F, Fernandes C. Semi-Preparative Separation, Absolute Configuration, Stereochemical Stability and Effects on Human Neuronal Cells of MDPV Enantiomers. Molecules. 2023;28(5):2121.

2. Silva B, Fernandes C, Guedes de Pinho P, Remião F. Chiral Resolution and Enantioselectivity of Synthetic Cathinones: A Brief Review. J Anal Toxicol. 2018;42(1):17-24.

3. Silva B, Silva R, Fernandes C, Guedes de Pinho P, Remião F. Enantioselectivity on the absorption of methylone and pentedrone using Caco-2 cell line: Development and validation of an UHPLC method for cathinones quantification. Toxicol Appl Pharmacol. 2020;395:114970.

4. Almeida AS, Silva B, Pinho PG, Remião F, Fernandes C. Synthetic Cathinones: Recent Developments, Enantioselectivity Studies and Enantioseparation Methods. Molecules. 2022;27(7).

5. Almeida AS, Silva B, Remião F, Fernandes C. Assessment of the Permeability of 3,4-Methylenedioxypyrovalerone (MDPV) across the Caco-2 Monolayer for Estimation of Intestinal Absorption and Enantioselectivity. Int J Mol Sci. 2023;24(3):2680.

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Published

2023-04-21

How to Cite

Almeida, A. S., Silva, B., Remião, F., & Fernandes, C. (2023). In vitro permeability of MDPV across Caco-2 cells for assessment of intestinal absorption and enantioselectivity. Scientific Letters, 1(Sup 1). https://doi.org/10.48797/sl.2023.61

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Section

Oral Communications

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