UPLC-MS/MS Method for Simultaneous Determination of 14 Antimicrobials in Human Plasma and Cerebrospinal Fluid: Application to Therapeutic Drug Monitoring.

Huiting Sun,Xueke Tian,Jing Yang,Han Xing,Xiaojian Zhang,Peile Wang,Mohamed Abdel-Rehim

doi:10.1155/2022/7048605

Abstract

Pharmacokinetics/pharmacodynamics is the foundation for guiding the rational application of antibiotics in clinical practice, so it is necessary to establish quantitative methods for accurate drug concentration determination. This study aimed to develop a rapid and simple ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous quantification of 14 antibiotics (amikacin, etimicin, ceftazidime, cefepime, cefoperazone, ceftriaxone, daptomycin, latamoxef, linezolid, meropenem, biapenem, ampicillin, norvancomycin, and vancomycin) in human plasma and cerebrospinal fluid. Antibiotics were chromatographically separated on a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) via gradient elution within 3 minutes and were monitored using positive ion fitted with multiple reaction monitoring. The lower limit of quantification was 0.05–2.0 μg·mL−1. The method was verified according to the FDA bioanalysis method validation guidelines, which showed excellent accuracy (from 86.75% to 110.85%) and precision (from 0.46% to 10.97%). At last, this method was successfully applied to therapeutic drug monitoring in 113 patients under antibiotics treatment.

Highlights

Central nervous system (CNS) infection is one of the most serious infections. e blood-brain barrier surrounding CNS and the emergence of multiple drug-resistant bacteria in recent years pose a therapeutic challenge for treating CNS infections [1, 2]
Individualizing antibiotic dosing via therapeutic drug monitoring (TDM) should be considered to maximize therapeutic success and reduce the generation of resistant bacteria [4, 5]. erefore, it is necessary to establish a reliable quantitative method to monitor the antibiotic concentrations in plasma and cerebrospinal fluid (CSF)
E aim of this study was to develop and validate an LCMS method for simultaneous determination of 14 antibiotics frequently used for the treatment of CNS bacterial infections in human plasma and CSF

Summary

Introduction

Central nervous system (CNS) infection is one of the most serious infections. e blood-brain barrier surrounding CNS and the emergence of multiple drug-resistant bacteria in recent years pose a therapeutic challenge for treating CNS infections [1, 2]. Most methods were based on time-consuming sample preparation procedures, covered a few or a class of antibiotics, and only measured drug concentration in blood or long analysis time [10,11,12,13,14,15]. Erefore, it is necessary to develop a simple and rapid method to cover frequently used antibiotics in Journal of Analytical Methods in Chemistry both blood and infection sites to assist TDM in routine laboratory practice. E aim of this study was to develop and validate an LCMS method for simultaneous determination of 14 antibiotics frequently used for the treatment of CNS bacterial infections (amikacin, etimicin, ceftazidime, cefepime, cefoperazone, ceftriaxone, daptomycin, latamoxef, linezolid, meropenem, biapenem, ampicillin, norvancomycin, and vancomycin) in human plasma and CSF. After meeting all the requirements in the bioanalytical guidance, the approach was applied for the TDM of antibiotics in patients, especially those with central system infection

Materials and Methods

Results and Discussion

Method Validation

Norvancomycin 20