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

2020 ◽  
Vol 42 (5) ◽  
pp. 716-723 ◽  
Author(s):  
Peile Wang ◽  
Qiwen Zhang ◽  
Zifei Qin ◽  
Han Xing ◽  
Min Xu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Liquid Chromatography ◽  
Therapeutic Drug Monitoring ◽  
Tandem Mass Spectrometry ◽  
Drug Monitoring ◽  
Analytical Method ◽  
Therapeutic Drug ◽  
Tandem Mass

scholarly journals Multiplex Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Therapeutic Drug Monitoring of Ribavirin, Boceprevir, and Telaprevir

2013 ◽  
Vol 57 (7) ◽  
pp. 3147-3158 ◽  
Author(s):  
Manel Aouri ◽  
Darius Moradpour ◽  
Matthias Cavassini ◽  
Thomas Mercier ◽  
Thierry Buclin ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Hepatitis C ◽  
Therapeutic Drug Monitoring ◽  
Tandem Mass Spectrometry ◽  
Antiviral Therapy ◽  
Drug Monitoring ◽  
Reversed Phase ◽  
Therapeutic Drug ◽  
Tandem Mass

ABSTRACTNew directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. However, an assay for the simultaneous analysis of RBV and DAAs constitutes an analytical challenge because of the large differences in polarity among these drugs, ranging from hydrophilic (RBV) to highly lipophilic (telaprevir [TVR]). Moreover, TVR is characterized by erratic behavior on standard octadecyl-based reversed-phase column chromatography and must be separated from VRT-127394, its inactive C-21 epimer metabolite. We have developed a convenient assay employing simple plasma protein precipitation, followed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of levels of RBV, boceprevir, and TVR, as well as its metabolite VRT-127394, in plasma. This new, simple, rapid, and robust HPLC-MS/MS assay offers an efficient method of real-time TDM aimed at maximizing efficacy while minimizing the toxicity of antiviral therapy.

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