{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:50:18Z","timestamp":1792000218244,"version":"4.4.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre","doi-asserted-by":"crossref","award":["2020\/37\/N\/NZ4\/03903"],"award-info":[{"award-number":["2020\/37\/N\/NZ4\/03903"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical University of Bialystok, Poland","award":["B.SUB.23.601"],"award-info":[{"award-number":["B.SUB.23.601"]}]},{"name":"Medical University of Bialystok, Poland","award":["B.SUB.23.601"],"award-info":[{"award-number":["B.SUB.23.601"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec>\n<jats:title>Purpose<\/jats:title>\n<jats:p>Statins are the most commonly used drugs worldwide. Besides a significant decrease in cardiovascular diseases (CVDs) risk, the use of statins is also connected with a broad beneficial pleiotropic effect. At the same time, it is burdened with different side effects. The most common ones are muscle issues (from mild myalgia to rhabdomyolysis). The mechanisms of many of them are still unclear. Therefore, an analytical method for the determination of simvastatin (SIM) and its main metabolite (the hydroxy acid form \u2013 SIMA) in muscle tissue was developed.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Muscle samples were homogenized with ammonium acetate buffer using the bead mill homogenizer, and then statins were extracted with a mixture of methanol and ethanol. Prepared samples were analyzed with liquid chromatography (using a reverse-phase column with a gradient elution) combined with the mass spectrometer which was operated in a multiple reaction monitoring mode.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The assay was linear over a 0.1\u20135\u2009ng\/mL range for both statin forms. Inter- and intra-day precision and accuracy were characterized. The method was considered precise (with the following relative standard deviation values: 6.0\u20136.9% for SIM, and 8.1\u201312.9% for SIMA) and accurate (with the following mean accuracies: 91.4\u2013100.1% for SIM, and 102.2\u2013115.4% for SIMA). The extraction efficiency was evaluated by recovery determination (76% for SIM, and 99% for SIMA). Moreover, the matrix effect was calculated with the following results: 87% for SIM, and 139% for SIMA. The proposed method was applied for SIM and SIMA determination in skeletal muscle tissues obtained from statin-treated patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The obtained results proved that the method may be a useful tool for explaining muscle effects related to statin therapy.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0322808","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T17:34:28Z","timestamp":1746466468000},"page":"e0322808","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of an LC-MS method for the determination of simvastatin and its hydroxy acid form in muscle tissue and method application"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5063-1500","authenticated-orcid":true,"given":"Ewa","family":"Paszkowska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6639-2823","authenticated-orcid":true,"given":"Karolina","family":"Pietrowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steen","family":"Larsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Fornal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Ciborowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"issue":"34","key":"pone.0322808.ref001","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.1093\/eurheartj\/ehac015","article-title":"Prevalence of statin intolerance: a meta-analysis","volume":"43","author":"I Byty\u00e7i","year":"2022","journal-title":"Eur Heart J"},{"issue":"10355","key":"pone.0322808.ref002","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/S0140-6736(22)01545-8","article-title":"Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials","volume":"400","author":"Cholesterol Treatment Trials Collaboration.","year":"2022","journal-title":"Lancet"},{"issue":"1","key":"pone.0322808.ref003","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1038\/s41467-022-30060-w","article-title":"Statin therapy inhibits fatty acid synthase via dynamic protein modifications","volume":"13","author":"AG Trub","year":"2022","journal-title":"Nat Commun"},{"issue":"6","key":"pone.0322808.ref004","doi-asserted-by":"crossref","first-page":"388-405.e6","DOI":"10.1016\/j.medj.2022.04.007","article-title":"Heterogeneity in statin responses explained by variation in the human gut microbiome","volume":"3","author":"T Wilmanski","year":"2022","journal-title":"Med"},{"issue":"21","key":"pone.0322808.ref005","doi-asserted-by":"crossref","first-page":"11687","DOI":"10.3390\/ijms222111687","article-title":"Statin-associated myopathy: emphasis on mechanisms and targeted therapy","volume":"22","author":"P Vinci","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"25","key":"pone.0322808.ref006","first-page":"2982","article-title":"Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study","volume":"76","author":"GA Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"pone.0322808.ref007","doi-asserted-by":"crossref","first-page":"222","DOI":"10.2174\/1570161116666180817155058","article-title":"The pleiotropic effects of statins - 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