{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:55:44Z","timestamp":1767837344768,"version":"3.49.0"},"reference-count":24,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fund of the Jilin Provincial Department of Science and Technology","award":["YDZJ202202CXJD050"],"award-info":[{"award-number":["YDZJ202202CXJD050"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Vancomycin (VAN), meropenem (MER), and valproate (VPA) are commonly used to treat intracranial infection post-craniotomy and prevent associated epilepsy. To monitor their levels, we developed a novel bioassay based on liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) for simultaneous determination of these three drugs in human serum and cerebrospinal fluid (CSF). Sample preparation by protein precipitation using acetonitrile was followed by HPLC on a Zorbax 300SB-C8 column (150 mm \u00d7 4.6 mm, 5 \u03bcm) maintained at 40 \u00b0C. The lower limit of quantification (LLOQ) was 5 ng\/mL for MER, 0.1 \u03bcg\/mL for VAN, and 1 \u03bcg\/mL for VPA in serum and 50 ng\/mL for MER, 1 \u03bcg\/mL for VAN, and 2 \u03bcg\/mL for VPA in CSF. This method was validated with satisfactory linearity, sensitivity, precision, accuracy, recovery, matrix effects, and stability for all analytes. The assay was then successfully applied to evaluate VPA, MER, and VAN levels in serum and CSF from patients with intracranial infection administrated by intrathecal injection. Compared with intravenous injections, an intrathecal injection can provide sufficient therapeutic effects even if the CSF levels did not reach the effective concentration reported. Our method provided a detection tool to study the effective concentrations of these three drugs in CSF from patients administered via intrathecal injection.<\/jats:p>","DOI":"10.3390\/molecules28062439","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T02:08:14Z","timestamp":1678241294000},"page":"2439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A High-Performance Liquid Chromatography\u2014Mass Spectrometry Method for Simultaneous Determination of Vancomycin, Meropenem, and Valproate in Patients with Post-Craniotomy Infection"],"prefix":"10.3390","volume":"28","author":[{"given":"Yuting","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun 130021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun 130021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumei","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun 130021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun 130021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s12098-017-2477-z","article-title":"Bacterial Infections of the Central Nervous System","volume":"86","author":"Suthar","year":"2019","journal-title":"Indian J. Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"ofab216","DOI":"10.1093\/ofid\/ofab216","article-title":"Ventriculitis: A Severe Complication of Central Nervous System Infections","volume":"8","author":"Revest","year":"2021","journal-title":"Open Forum Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7849","DOI":"10.1038\/srep07849","article-title":"Biodegradable vancomycin-eluting poly[(d,l)-lactide-co-glycolide] nanofibres for the treatment of postoperative central nervous system infection","volume":"5","author":"Tseng","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Schneider, F., and Gessner, A. (2022). Efficacy of Vancomycin and Meropenem in Central Nervous System Infections in Children and Adults: Current Update. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020173"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.nbd.2018.06.017","article-title":"In search of antiepileptogenic treatments for post-traumatic epilepsy","volume":"123","author":"Saletti","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2174\/1570159X15666171109143654","article-title":"Relevance of CYP2C9 Function in Valproate Therapy","volume":"17","author":"Monostory","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jen.2018.11.003","article-title":"Valproate Poisoning","volume":"45","author":"Mekonnen","year":"2019","journal-title":"J. Emerg. Nurs."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1089\/sur.2018.238","article-title":"Vancomycin Enema in the Treatment of Clostridium difficile Infection","volume":"20","author":"Fawley","year":"2019","journal-title":"Surg. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1097\/FTD.0000000000000650","article-title":"Preanalytical Stability of Piperacillin, Tazobactam, Meropenem, and Ceftazidime in Plasma and Whole Blood Using Liquid Chromatography-Tandem Mass Spectrometry","volume":"41","author":"Mortensen","year":"2019","journal-title":"Ther. Drug Monit."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e15139","DOI":"10.1097\/MD.0000000000015139","article-title":"A case report of intraventricular and intrathecal tigecycline infusions for an extensively drug-resistant intracranial Acinetobacter baumannii infection","volume":"98","author":"Deng","year":"2019","journal-title":"Medicine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1186\/s13054-016-1523-y","article-title":"Cerebrospinal fluid penetration of meropenem in neurocritical care patients with proven or suspected ventriculitis: A prospective observational study","volume":"20","author":"Blassmann","year":"2016","journal-title":"Crit. Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"113273","DOI":"10.1016\/j.jpba.2020.113273","article-title":"A liquid chromatography-tandem mass spectrometry platform for the routine therapeutic drug monitoring of 14 antibiotics: Application to critically ill pediatric patients","volume":"186","author":"Barco","year":"2022","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"122151","DOI":"10.1016\/j.jchromb.2020.122151","article-title":"Validation of a simple and economic HPLC-UV method for the simultaneous determination of vancomycin, meropenem, piperacillin and tazobactam in plasma samples","volume":"1148","author":"Milla","year":"2020","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lipska, K., and Gumieniczek, A. (2021). HPLC-UV and GC-MS Methods for Determination of Chlorambucil and Valproic Acid in Plasma for Further Exploring a New Combined Therapy of Chronic Lymphocytic Leukemia. Molecules, 26.","DOI":"10.3390\/molecules26102903"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.jpba.2008.06.012","article-title":"Simultaneous determination of vancomycin and ceftazidime in cerebrospinal fluid in craniotomy patients by high-performance liquid chromatography","volume":"48","author":"Ye","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1044234","DOI":"10.3389\/fphar.2022.1044234","article-title":"An LC-MS\/MS method for the simultaneous determination of 18 antibacterial drugs in human plasma and its application in therapeutic drug monitoring","volume":"13","author":"Lu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/clinchem\/41.2.256","article-title":"External quality assessment in clinical neurochemistry: Survey of analysis for cerebrospinal fluid (CSF) proteins based on CSF\/serum quotients","volume":"41","author":"Reiber","year":"1995","journal-title":"Clin. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/jcpt.13369","article-title":"Meropenem use and therapeutic drug monitoring in clinical practice: A literature review","volume":"46","author":"Steffens","year":"2021","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10096-016-2803-9","article-title":"Drug concentrations in the serum and cerebrospinal fluid of patients treated with norvancomycin after craniotomy","volume":"36","author":"Wu","year":"2017","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_20","first-page":"233","article-title":"Therapeutic drug monitoring of valproate","volume":"65","author":"Tribut","year":"2010","journal-title":"Therapie"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"218.e211-215","DOI":"10.1016\/j.jcrc.2014.09.020","article-title":"The methodology and pharmacokinetics study of intraventricular administration of vancomycin in patients with intracranial infections after craniotomy","volume":"30","author":"Chen","year":"2015","journal-title":"J. Crit. Care"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1128\/CMR.00007-10","article-title":"Penetration of drugs through the blood-cerebrospinal fluid\/BBB for treatment of central nervous system infections","volume":"23","author":"Nau","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/s12028-012-9784-z","article-title":"Systematic review of efficacy, pharmacokinetics, and administration of intraventricular vancomycin in adults","volume":"20","author":"Ng","year":"2014","journal-title":"Neurocrit. Care"},{"key":"ref_24","unstructured":"(2018, May 24). Bioanalytical Method Validation Guidance for Industry, Available online: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/bioanalytical-method-validation-guidance-industry."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/6\/2439\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:49:56Z","timestamp":1760122196000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/6\/2439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,7]]},"references-count":24,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["molecules28062439"],"URL":"https:\/\/doi.org\/10.3390\/molecules28062439","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,7]]}}}