Therapeutic drug monitoring of polymyxin B by LC-MS/MS in plasma and urine.

Background: A robust and rapid method for therapeutic drug monitoring (TDM) is urgently needed for polymyxin B, which is a last-line antibiotic for multidrug-resistant gram-negative bacteria infection. Methodology: A 3-min run of LC-MS/MS method was established to determine the main components of polymyxin B (polymyxin B1 and B2) in human plasma or urine. Solid-phase extraction was employed to eliminate the matrix effect from complicated samples from patients. Results: The calibration range was 0.050-5.00 and 0.0110-0.549 μg/ml for polymyxin B1 and B2, respectively, in plasma and urine. The precision and accuracy of quality controls, matrix effect, extraction recovery and stability were all validated and satisfied with the ICH requirements. The method was successfully applied to a pharmacokinetic study in healthy subjects and TDM in patients. Conclusion: The rapid LC-MS/MS method was validated for polymyxin B in plasma and urine, and robust for TDM.