A High-Performance Liquid Chromatography—Mass Spectrometry Method for Simultaneous Determination of Vancomycin, Meropenem, and Valproate in Patients with Post-Craniotomy Infection

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.