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Although many reports have reported the drug\u2013drug interactions of VPA, no study has focused on the influence of carbapenems (CBPMs) on VPA's active metabolites. An LC\u2013MS\/MS method for determining VPA and its six metabolites (3\u2010hydroxy valproic acid, 4\u2010hydroxy valproic acid, 2\u2010propyl\u20102\u2010pentenoic acid, 2\u2010propyl\u20104\u2010pentenoic acid, 3\u2010keto valproic acid, and 2\u2010propylglutaric acid) in human serum was established and applied to evaluate the drug\u2013drug interaction with CBPMs in epileptic patients. The stable isotope valproic acid\u2010d6 was used as an internal standard. Analytes in serum samples (50\u2009\u03bcl) were isolated using a Kinetex C<jats:sub>18<\/jats:sub> column (3\u00a0\u00d7\u2009100\u2009mm, 2.6\u00a0\u03bcm) and detected via negative electrospray ionization after protein precipitation. It was linear (<jats:italic>r<\/jats:italic>\u00a0&gt;\u20090.99) over the calibration range for different analytes. The accuracy was 91.44\u2013110.92%, and the precision was less than 9.98%. The matrix effect, recovery, and stability met the acceptance criteria. According to the data collected from 150 epileptic patients, the concentration\u2013dose ratio for VPA and its metabolites decreased with CBPM polytherapy. This method is simple and rapid with great accuracy and precision. It is suitable for routine clinical analysis of VPA and its metabolites in human serum.<\/jats:p>","DOI":"10.1002\/bmc.5572","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T11:49:53Z","timestamp":1671104993000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Determination of valproic acid and its six metabolites in human serum using LC\u2013MS\/MS and application to interaction with carbapenems in epileptic patients"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4617-9232","authenticated-orcid":false,"given":"Xuping","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacy The First People's Hospital of Changzhou\/The Third Affiliated Hospital of Soochow University  Changzhou 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