Development and validation of an UPLC-MS/MS method for simultaneous determination of meropenem and its open-ring

XiangLong Chen1, Jinhui Xu1, Chengliang Wang1

  • 1Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China.

Insights

A new LC-MS/MS method accurately measures meropenem (MER) and its metabolite (ORM) in human serum and cerebrospinal fluid (CSF). This supports therapeutic drug monitoring for central nervous system (CNS) infections.

Area of Science:

  • Pharmacokinetics
  • Analytical Chemistry
  • Infectious Diseases

Background:

  • Central nervous system (CNS) infections necessitate effective antibiotic concentrations at the infection site.
  • Meropenem (MER), a critical antibiotic, exhibits poor cerebrospinal fluid (CSF) penetration and degrades into an inactive open-ring metabolite (ORM).
  • Accurate quantification of MER and ORM in biological matrices is essential for optimizing treatment.

Purpose of the Study:

  • To develop and validate a simple, sensitive, and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.
  • To simultaneously determine meropenem (MER) and its inactive metabolite (ORM) concentrations in human serum and CSF.
  • To enable therapeutic drug monitoring for MER in patients with CNS infections.

Main Methods:

  • Development of a rapid LC-MS/MS assay utilizing an Agela Venusil MP C18 column.
  • Optimization of sample preparation using acetonitrile for protein precipitation and mobile phase.
  • Validation of the method according to the ICH M10 guideline for accuracy and precision.

Main Results:

  • Successful simultaneous determination of MER and ORM in human serum and CSF samples.
  • Demonstrated method sensitivity, simplicity, and speed for routine clinical application.
  • Reported, for the first time, open-ring metabolite (ORM) concentrations in human CSF.

Conclusions:

  • The validated LC-MS/MS method is a valuable tool for quantifying MER and ORM in serum and CSF.
  • This assay facilitates therapeutic drug monitoring of meropenem in patients with CNS infections.
  • The findings contribute to a better understanding of meropenem pharmacokinetics in the CNS.

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