Rapid and sensitive method for measuring the plasma concentration of doxorubicin and its metabolites

Abstract

Doxorubicin is an anti-cancer drug with a wide therapeutic range. However, it and its metabolites cause severe side effects, limiting its clinical use. Therefore, measuring the plasma concentration of doxorubicin and its metabolites is important to study the dosing regimen of doxorubicin. We developed a rapid and sensitive method by ultra-high-performance liquid chromatography with fluorescent detection for measuring the plasma concentration of doxorubicin and its metabolites in small volumes (around 10 μL), enabling repeated measurements from the same mouse. The sensitivity of 7-deoxydoxorubicinolone, a major metabolite of doxorubicin, increased about 5 times than those ever reported using conventional HPLC, and the run time was within 3 min. The area under the curve (AUC 0-24h) of doxorubicin was 5.9 μg h/mL similar to the value of 4.16 μg h/mL obtained previously using a conventional HPLC method. This method would provide information that could be used to refine the therapeutic approach to doxorubicin use. © 2012 The Pharmaceutical Society of Japan.