Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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A Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneously Determining Meropenem and Linezolid in Blood and Cerebrospinal Fluid

  • Joanna Berska (Department of Clinical Biochemistry, Institute of Pediatrics, Jagiellonian University Medical College) ;
  • Jolanta Bugajska (Department of Clinical Biochemistry, Institute of Pediatrics, Jagiellonian University Medical College) ;
  • Krystyna Sztefko (Department of Clinical Biochemistry, Institute of Pediatrics, Jagiellonian University Medical College)
  • Received : 2023.06.21
  • Accepted : 2023.09.14
  • Published : 2024.03.01
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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.

Keywords

Acknowledgement

The study was supported by a grand from Jagiellonian University (No. N41/DBS/000471).

References

  1. Mian P, Flint RB, Tibboel D, van den Anker JN, Allegaert K, Koch BCP. Therapeutic drug monitoring in neonates: what makes them unique? Curr Pharm Des 2017;23:5790-800. https://doi.org/10.2174/1381612823666170926143820
  2. Wicha SG, Kees MG, Kuss J, Kloft C. Pharmacodynamic and response surface analysis of linezolid or vancomycin combined with meropenem against Staphylococcus aureus. Pharm Res 2015;32:2410-8. https://doi.org/10.1007/s11095-015-1632-3
  3. Tan YC, Gill AK, Kim KS. Treatment strategies for central nervous system infections: an update. Expert Opin Pharmacother 2015;16:187-203. https://doi.org/10.1517/14656566.2015.973851
  4. Schneider F, Gessner A, El-Najjar N. Efficacy of vancomycin and meropenem in central nervous system infections in children and adults: current update. Antibiotics (Basel) 2022;11:173. https://doi.org/10.3390/antibiotics11020173
  5. U.S Food and Drug Administration, Bioanalytical method validation guidance for industry. https://www.fda.gov/regulatory-information/searchfda-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. Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections. Clin Microbiol Rev 2010;23:858-83. https://doi.org/10.1128/CMR.00007-10
  8. Tsona A, Metallidis S, Foroglou N, Selviaridis P, Chrysanthidis T, Lazaraki G, et al. Linezolid penetration into cerebrospinal fluid and brain tissue. J Chemother 2010;22:17-9. https://doi.org/10.1179/joc.2010.22.1.17
  9. Germovsek E, Lutsar I, Kipper K, Karlsson MO, Planche T, Chazallon C, et al. Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies. J Antimicrob Chemother 2018;73:1908-16. https://doi.org/10.1093/jac/dky128
  10. Cojutti P, Maximova N, Crichiutti G, Isola M, Pea F. 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 2015;70:198-206. https://doi.org/10.1093/jac/dku337
  11. Roth T, Fiedler S, Mihai S, Parsch H. Determination of meropenem levels in human serum by high-performance liquid chromatography with ultraviolet detection. Biomed Chromatogr 2017;31:e3880. https://doi.org/10.1002/bmc.3880
  12. Milla P, Ferrari F, Muntoni E, Sartori M, Ronco C, Arpicco S. 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 2020;1148:122151. https://doi.org/10.1016/j.jchromb.2020.122151
  13. Decosterd LA, Mercier T, Ternon B, Cruchon S, Guignard N, Lahrichi S, et al. 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 2020;1157:122160. https://doi.org/10.1016/j.jchromb.2020.122160
  14. Phillips OA, Abdel-Hamid ME, Al-Hassawi NA. Determination of linezolid in human plasma by LC-MS-MS. Analyst 2001;126:609-14. https://doi.org/10.1039/b100076o
  15. Rehm S and Rentsch KM. HILIC LC-MS/MS method for the quantification of cefepime, imipenem and meropenem. J Pharm Biomed Anal 2020;186:113289. https://doi.org/10.1016/j.jpba.2020.113289
  16. Zander J, Maier B, Suhr A, Zoller M, Frey L, Teupser D, et al. 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 2015;53:781-91. https://doi.org/10.1515/cclm-2014-0746
  17. Paal M, Zoller M, Schuster C, Vogeser M, Schütze G. 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 2018;152:102-10. https://doi.org/10.1016/j.jpba.2018.01.031
  18. Ferrari D, Ripa M, Premaschi S, Banfi G, Castagna A, Locatelli M. LCMS/MS method for simultaneous determination of linezolid, meropenem, piperacillin and teicoplanin in human plasma samples. J Pharm Biomed Anal 2019;169:11-8. https://doi.org/10.1016/j.jpba.2019.02.037
  19. Barco S, Bandettini R, Maffia A, Tripodi G, Castagnola E, Cangemi G. Quantification of piperacillin, tazobactam, meropenem, ceftazidime, and linezolid in human plasma by liquid chromatography/tandem mass spectrometry. J Chemother 2015;27:343-7. https://doi.org/10.1179/1973947814Y.0000000209
  20. Sun H, Xing H, Tian X, Zhang X, Yang J, Wang P. 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;2022:7048605. https://doi.org/10.1155/2022/7048605