Wang Peile, Zhang Qiwen, Qin Zifei, Xing Han, Xu Min, Pei Hui, Yang Jing, Zhang Xiaojian
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University.
Henan Key Laboratory of Precision Clinical Pharmacy, The First Affiliated Hospital of Zhengzhou University; and.
Ther Drug Monit. 2020 Oct;42(5):716-723. doi: 10.1097/FTD.0000000000000754.
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.
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.
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.
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.
多黏菌素B被用作多重耐药革兰氏阴性菌感染的最后治疗手段。本研究旨在开发并验证一种简单且可靠的液相色谱-串联质谱分析方法，用于监测血浆和脑脊液（CSF）中多黏菌素B1和B2的治疗药物浓度。
血浆和脑脊液中的多黏菌素B1和B2在Thermo Hypersil GOLD aQ C18柱上进行色谱分离，并采用电喷雾电离模式结合多反应监测进行检测。从15例接受多黏菌素B治疗的患者中采集用于药代动力学分析的血液和脑脊液样本。
校准曲线显示，血浆和脑脊液中多黏菌素B1在0.2 - 10 mcg/mL范围内、B2在0.05 - 2.5 mcg/mL范围内具有可接受的线性。经验证后，根据美国食品药品监督管理局（FDA）的方法验证指南，该方法应用于一项临床研究中100多个样本的多黏菌素B1和B2定量分析。
首次开发并验证了一种简单且可靠的方法来测定人脑脊液中的多黏菌素B1和B2，该方法具有良好的灵敏度和特异性，并成功应用于中国患者的多黏菌素B药代动力学分析和治疗监测。
