Xiaofen Liu1,2,3, Zhenwei Yu4, Yu Wang1,2,3, Hailan Wu1,2,3, Xingchen Bian1,2,3, Xin Li1,2,3, Yaxin Fan1,2,3, Beining Guo1,2,3, Jing Zhang1,2,3,5. 1. Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, PR China. 2. Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of the People's Republic of China, Shanghai 200040, PR China. 3. National Clinical Research Center for Aging & Medicine, Huashan Hospital, Fudan University, Shanghai 200040, PR China. 4. Sir Run Run Shaw Hospital, College of Medicine, Zhenjiang University, 3rd East Qingchun Road, Hangzhou 310016, PR China. 5. Phase I Clinical Trial Center, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
Abstract
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.
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.
Entities:
Keywords:
LC–MS/MS; pharmacokinetics; polymyxins; therapeutic drug monitoring