In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method

Abstract Low-dose aspirin (ASA) is used to prevent cardiovascular events. The most commonly used formulation is enteric-coated ASA (EC-ASA) that may be absorbed more slowly and less efficiently in some patients. To uncover these “non-responders” patients, the availability of proper analytical method...

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Autores principales:	Michele Dei Cas, Jessica Rizzo, Mariangela Scavone, Eti Femia, Gian Marco Podda, Elena Bossi, Monica Bignotto, Sabrina Caberlon, Marco Cattaneo, Rita Paroni
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a2dabf8d85284cceb2903a0e52a60ee8
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spelling	oai:doaj.org-article:a2dabf8d85284cceb2903a0e52a60ee82021-12-02T17:15:32ZIn-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method10.1038/s41598-021-89671-w2045-2322https://doaj.org/article/a2dabf8d85284cceb2903a0e52a60ee82021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89671-whttps://doaj.org/toc/2045-2322Abstract Low-dose aspirin (ASA) is used to prevent cardiovascular events. The most commonly used formulation is enteric-coated ASA (EC-ASA) that may be absorbed more slowly and less efficiently in some patients. To uncover these “non-responders” patients, the availability of proper analytical methods is pivotal in order to study the pharmacodynamics, the pharmacokinetics and the metabolic fate of ASA. We validated a high-throughput, isocratic reversed-phase, negative MRM, LC–MS/MS method useful for measuring circulating ASA and salicylic acid (SA) in blood and plasma. ASA-d4 and SA-d4 were used as internal standards. The method was applied to evaluate: (a) the "in vitro" ASA degradation by esterases in whole blood and plasma, as a function of time and concentration; (b) the "in vivo" kinetics of ASA and SA after 7 days of oral administration of EC-ASA or plain-ASA (100 mg) in healthy volunteers (three men and three women, 37–63 years). Parameters of esterases activity were V max 6.5 ± 1.9 and K m 147.5 ± 64.4 in plasma, and V max 108.1 ± 20.8 and K m 803.2 ± 170.7 in whole blood. After oral administration of the two formulations, t max varied between 3 and 6 h for EC-ASA and between 0.5 and 1.0 h for plain-ASA. Higher between-subjects variability was seen after EC-ASA, and one subject had a delayed absorption over eight hours. Plasma AUC was 725.5 (89.8–1222) for EC-ASA, and 823.1(624–1196) ng h/mL (median, 25–75% CI) for plain ASA. After the weekly treatment, serum levels of TxB2 were very low (< 10 ng/mL at 24 h from the drug intake) in all the studied subjects, regardless of the formulation or the t max. This method proved to be suitable for studies on aspirin responsiveness.Michele Dei CasJessica RizzoMariangela ScavoneEti FemiaGian Marco PoddaElena BossiMonica BignottoSabrina CaberlonMarco CattaneoRita ParoniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michele Dei Cas Jessica Rizzo Mariangela Scavone Eti Femia Gian Marco Podda Elena Bossi Monica Bignotto Sabrina Caberlon Marco Cattaneo Rita Paroni In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method
description	Abstract Low-dose aspirin (ASA) is used to prevent cardiovascular events. The most commonly used formulation is enteric-coated ASA (EC-ASA) that may be absorbed more slowly and less efficiently in some patients. To uncover these “non-responders” patients, the availability of proper analytical methods is pivotal in order to study the pharmacodynamics, the pharmacokinetics and the metabolic fate of ASA. We validated a high-throughput, isocratic reversed-phase, negative MRM, LC–MS/MS method useful for measuring circulating ASA and salicylic acid (SA) in blood and plasma. ASA-d4 and SA-d4 were used as internal standards. The method was applied to evaluate: (a) the "in vitro" ASA degradation by esterases in whole blood and plasma, as a function of time and concentration; (b) the "in vivo" kinetics of ASA and SA after 7 days of oral administration of EC-ASA or plain-ASA (100 mg) in healthy volunteers (three men and three women, 37–63 years). Parameters of esterases activity were V max 6.5 ± 1.9 and K m 147.5 ± 64.4 in plasma, and V max 108.1 ± 20.8 and K m 803.2 ± 170.7 in whole blood. After oral administration of the two formulations, t max varied between 3 and 6 h for EC-ASA and between 0.5 and 1.0 h for plain-ASA. Higher between-subjects variability was seen after EC-ASA, and one subject had a delayed absorption over eight hours. Plasma AUC was 725.5 (89.8–1222) for EC-ASA, and 823.1(624–1196) ng h/mL (median, 25–75% CI) for plain ASA. After the weekly treatment, serum levels of TxB2 were very low (< 10 ng/mL at 24 h from the drug intake) in all the studied subjects, regardless of the formulation or the t max. This method proved to be suitable for studies on aspirin responsiveness.
format	article
author	Michele Dei Cas Jessica Rizzo Mariangela Scavone Eti Femia Gian Marco Podda Elena Bossi Monica Bignotto Sabrina Caberlon Marco Cattaneo Rita Paroni
author_facet	Michele Dei Cas Jessica Rizzo Mariangela Scavone Eti Femia Gian Marco Podda Elena Bossi Monica Bignotto Sabrina Caberlon Marco Cattaneo Rita Paroni
author_sort	Michele Dei Cas
title	In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method
title_short	In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method
title_full	In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method
title_fullStr	In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method
title_full_unstemmed	In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method
title_sort	in-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a2dabf8d85284cceb2903a0e52a60ee8
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In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method

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