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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
A High-Performance Liquid Chromatography-Mass Spectrometry Method for Simultaneous Determination of Vancomycin,
Yuting Jin1, Qiang Sun1, Yumei Pei1
1Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun 130021, China.
Abstract:
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-tandem mass spectrometry (LC-MS/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 × 4.6 mm, 5 μm) maintained at 40 °C. The lower limit of quantification (LLOQ) was 5 ng/mL for MER, 0.1 μg/mL for VAN, and 1 μg/mL for VPA in serum and 50 ng/mL for MER, 1 μg/mL for VAN, and 2 μg/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.
Insights
A new LC-MS/MS bioassay accurately measures vancomycin, meropenem, and valproate in serum and CSF. This tool aids in understanding drug efficacy for intracranial infections, especially with intrathecal administration.
Area of Science:
- Pharmacology and Toxicology
- Analytical Chemistry
- Neuroscience
Background:
- Intracranial infections post-craniotomy require treatment with vancomycin (VAN), meropenem (MER), and valproate (VPA).
- Monitoring drug levels in serum and cerebrospinal fluid (CSF) is crucial for effective treatment and epilepsy prevention.
- Existing methods may not be suitable for simultaneous quantification of these three drugs in both matrices.
Purpose of the Study:
- To develop and validate a novel bioassay for simultaneous determination of VAN, MER, and VPA.
- To quantify drug concentrations in human serum and CSF using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- To investigate drug levels in patients with intracranial infections receiving intrathecal injections.
Main Methods:
- Simultaneous quantification of VAN, MER, and VPA using LC-MS/MS.
- Sample preparation involved protein precipitation with acetonitrile.
- High-performance liquid chromatography (HPLC) was performed on a Zorbax 300SB-C8 column at 40 °C.
Main Results:
- The validated LC-MS/MS method demonstrated satisfactory linearity, sensitivity, precision, accuracy, recovery, matrix effects, and stability.
- Established lower limits of quantification (LLOQ) for MER, VAN, and VPA in both serum and CSF.
- Successfully applied the assay to evaluate drug levels in patients with intracranial infections treated with intrathecal injections.
Conclusions:
- The developed LC-MS/MS bioassay is a reliable tool for simultaneous measurement of VAN, MER, and VPA in serum and CSF.
- Intrathecal administration may achieve therapeutic effects even below reported effective CSF concentrations.
- This method facilitates research into optimal drug concentrations for intrathecal therapy in intracranial infections.
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