A Simple and Robust Liquid Chromatography With Tandem Mass Spectrometry Analytical Method for Therapeutic Drug Monitoring of Plasma and Cerebrospinal Fluid Polymyxin B1 and B2

Background: Polymyxin B is used as the last treatment resort for multidrug-resistant gram-negative bacterial infections. This study aimed to develop and validate a simple and robust liquid chromatography with tandem mass spectrometry analytical method for therapeutic drug monitoring of plasma and cerebrospinal fluid (CSF) polymyxin B1 and B2. Methods: Plasma and CSF polymyxin B1 and B2 were chromatographically separated on a Thermo Hypersil GOLD aQ C18 column and detected using electrospray ionization(+)mode coupled with multiple reaction monitoring. Blood and CSF samples for pharmacokinetic analysis were collected from 15 polymyxin B-treated patients. Results: The calibration curve showed acceptable linearity over 0.2-10 mcg/mL for polymyxin B1 and 0.05-2.5 mcg/mL for B2 in the plasma and CSF, respectively. After validation, according to the Food and Drug Administration (FDA) method validation guideline, this method was applied for polymyxin B1 and B2 quantification in over 100 samples in a clinical study. Conclusions: A simple and robust method to measure polymyxin B1 and B2 in human CSF was first exploited and validated with good sensitivity and specificity, and successfully applied in polymyxin B pharmacokinetic analysis and therapeutic monitoring in Chinese patients.