Ann Lab Med.  2024 Mar;44(2):174-178. 10.3343/alm.2023.0250.

A Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneously Determining Meropenem and Linezolid in Blood and Cerebrospinal Fluid

Affiliations
  • 1Department of Clinical Biochemistry, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland

Abstract

Antibiotic therapy requires appropriate dosage of drugs for effective treatment. Too low antibiotic concentrations may lead to treatment failure and the development of resistant pathogens, whereas overdosing may cause neurological side effects or hemolytic diseases. Meropenem and linezolid are used only in the treatment of serious infections or when other antibiotics are no longer effective as well as for treating central nervous system infections. It is difficult or sometimes even impossible to predict the relation between dosing of antibiotics and its cerebrospinal fluid (CSF) concentration; thus, a method of determining antibiotics not only in the blood but also in the CSF is needed. Analytical method validation is an integral part of good laboratory practice and ensures high accuracy of the results. We performed complete validation process according to the Food and Drug Administration and European Medicine Agency, covering the aspects precision, specificity, accuracy, recovery, limit of detection, limit of quantification, stability, carry-over, and matrix effects. Our liquid chromatography-tandem mass spectrometry method for the simultaneous measurement of meropenem and linezolid in different matrix meets all the acceptance criteria. The method was successfully applied to determine meropenem and linezolid concentrations in serum and CSF samples obtained from children treated with these antibiotics

Keyword

Antimicrobial agent; Blood; Cerebrospinal fluid; Linezolid; Liquid chromatography; Mass spectrometry; Meropenem; Validation study

Figure

  • Fig. 1 Chromatogram of spiked plasma sample at 1 µg/mL for meropenem and linezolid.


Reference

1. Mian P, Flint RB, Tibboel D, van den Anker JN, Allegaert K, Koch BCP. 2017; Therapeutic drug monitoring in neonates: what makes them unique? Curr Pharm Des. 23:5790–800. DOI: 10.2174/1381612823666170926143820. PMID: 28950825.
Article
2. Wicha SG, Kees MG, Kuss J, Kloft C. 2015; Pharmacodynamic and response surface analysis of linezolid or vancomycin combined with meropenem against Staphylococcus aureus. Pharm Res. 32:2410–8. DOI: 10.1007/s11095-015-1632-3. PMID: 25630818.
Article
3. Tan YC, Gill AK, Kim KS. 2015; Treatment strategies for central nervous system infections: an update. Expert Opin Pharmacother. 16:187–203. DOI: 10.1517/14656566.2015.973851. PMID: 25328149.
Article
4. Schneider F, Gessner A, El-Najjar N. 2022; Efficacy of vancomycin and meropenem in central nervous system infections in children and adults: current update. Antibiotics (Basel). 11:173. DOI: 10.3390/antibiotics11020173. PMID: 35203776. PMCID: PMC8868565.
Article
5. U.S Food and Drug Administration, Bioanalytical method validation guidance for industry. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioanalytical-method-validation-guidance-industry. Updated on May 2018.
6. European Medicines Agency. Guideline on bioanalytical method validation. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-bioanalytical-method-validation_en.pdf. Updated on July 2011.
7. Nau R, Sörgel F, Eiffert H. 2010; Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections. Clin Microbiol Rev. 23:858–83. DOI: 10.1128/CMR.00007-10. PMID: 20930076. PMCID: PMC2952976.
Article
8. Tsona A, Metallidis S, Foroglou N, Selviaridis P, Chrysanthidis T, Lazaraki G, et al. 2010; Linezolid penetration into cerebrospinal fluid and brain tissue. J Chemother. 22:17–9. DOI: 10.1179/joc.2010.22.1.17. PMID: 20227987.
Article
9. Germovsek E, Lutsar I, Kipper K, Karlsson MO, Planche T, Chazallon C, et al. 2018; Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies. J Antimicrob Chemother. 73:1908–16. DOI: 10.1093/jac/dky128. PMID: 29684147. PMCID: PMC6005047.
Article
10. Cojutti P, Maximova N, Crichiutti G, Isola M, Pea F. 2015; Pharmacokinetic/pharmacodynamic evaluation of linezolid in hospitalized paediatric patients: a step toward dose optimization by means of therapeutic drug monitoring and Monte Carlo simulation. J Antimicrob Chemother. 70:198–206. DOI: 10.1093/jac/dku337. PMID: 25182066.
Article
11. Roth T, Fiedler S, Mihai S, Parsch H. 2017; Determination of meropenem levels in human serum by high-performance liquid chromatography with ultraviolet detection. Biomed Chromatogr. 31:e3880. DOI: 10.1002/bmc.3880. PMID: 27797104.
Article
12. Milla P, Ferrari F, Muntoni E, Sartori M, Ronco C, Arpicco S. 2020; Validation of a simple and economic HPLC-UV method for the simultaneous determination of vancomycin, meropenem, piperacillin and tazobactam in plasma samples. J Chromatogr B Analyt Technol Biomed Life Sci. 1148:122151. DOI: 10.1016/j.jchromb.2020.122151. PMID: 32417718.
Article
13. Decosterd LA, Mercier T, Ternon B, Cruchon S, Guignard N, Lahrichi S, et al. 2020; Validation and clinical application of a multiplex high performance liquid chromatography - tandem mass spectrometry assay for the monitoring of plasma concentrations of 12 antibiotics in patients with severe bacterial infections. J Chromatogr B Analyt Technol Biomed Life Sci. 1157:122160. DOI: 10.1016/j.jchromb.2020.122160. PMID: 32891946.
Article
14. Phillips OA, Abdel-Hamid ME, Al-Hassawi NA. 2001; Determination of linezolid in human plasma by LC-MS-MS. Analyst. 126:609–14. DOI: 10.1039/b100076o. PMID: 11394301.
Article
15. Rehm S, Rentsch KM. 2020; HILIC LC-MS/MS method for the quantification of cefepime, imipenem and meropenem. J Pharm Biomed Anal. 186:113289. DOI: 10.1016/j.jpba.2020.113289. PMID: 32428767.
Article
16. Zander J, Maier B, Suhr A, Zoller M, Frey L, Teupser D, et al. 2015; Quantification of piperacillin, tazobactam, cefepime, meropenem, ciprofloxacin and linezolid in serum using an isotope dilution UHPLC-MS/MS method with semi-automated sample preparation. Clin Chem Lab Med. 53:781–91. DOI: 10.1515/cclm-2014-0746. PMID: 25301676.
Article
17. Paal M, Zoller M, Schuster C, Vogeser M, Schütze G. 2018; Simultaneous quantification of cefepime, meropenem, ciprofloxacin, moxifloxacin, linezolid and piperacillin in human serum using an isotope-dilution HPLC-MS/MS method. J Pharm Biomed Anal. 152:102–10. DOI: 10.1016/j.jpba.2018.01.031. PMID: 29414000.
Article
18. Ferrari D, Ripa M, Premaschi S, Banfi G, Castagna A, Locatelli M. 2019; LC-MS/MS method for simultaneous determination of linezolid, meropenem, piperacillin and teicoplanin in human plasma samples. J Pharm Biomed Anal. 169:11–8. DOI: 10.1016/j.jpba.2019.02.037. PMID: 30826487.
Article
19. Barco S, Bandettini R, Maffia A, Tripodi G, Castagnola E, Cangemi G. 2015; Quantification of piperacillin, tazobactam, meropenem, ceftazidime, and linezolid in human plasma by liquid chromatography/tandem mass spectrometry. J Chemother. 27:343–7. DOI: 10.1179/1973947814Y.0000000209. PMID: 25178412.
Article
20. Sun H, Xing H, Tian X, Zhang X, Yang J, Wang P. 2022; UPLC-MS/MS method for simultaneous determination of 14 antimicrobials in human plasma and cerebrospinal fluid: application to therapeutic drug monitoring. J Anal Methods Chem. 2022:7048605. DOI: 10.1155/2022/7048605. PMID: 35036023. PMCID: PMC8754666.
Article
Full Text Links
  • ALM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr