| Title: |
In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method |
| Authors: |
Michele Dei Cas, Jessica Rizzo, Mariangela Scavone, Eti Femia, Gian Marco Podda, Elena Bossi, Monica Bignotto, Sabrina Caberlon, Marco Cattaneo, Rita Paroni |
| Source: |
Scientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
| Publisher Information: |
Nature Portfolio, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Medicine
LCC:Science |
| Subject Terms: |
Medicine, Science |
| More Details: |
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 ( |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2045-2322 |
| Relation: |
https://doaj.org/toc/2045-2322 |
| DOI: |
10.1038/s41598-021-89671-w |
| Access URL: |
https://doaj.org/article/a2dabf8d85284cceb2903a0e52a60ee8 |
| Accession Number: |
edsdoj.2dabf8d85284cceb2903a0e52a60ee8 |
| Database: |
Directory of Open Access Journals |
