Quantification of Doxorubicin in Pegylated Polymer Micelles in Rat Plasma by Methanol Precipitation–Ultrasonic Emulsion Breaking Method and UPLC–MS–MS

• Published in: Chromatographia Vol. 74; no. 3-4; pp. 333 - 340
• Main Authors: Zhang, Wenping, Sun, Jin, Feng, Zhi, Su, Xiaonan, Zhu, Meng, Sui, Xiaofan, Liu, Yan, Tao, Mengying, Sun, Yunqiang, Chen, Guoliang, He, Zhonggui
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-08-2011; Springer
• Subjects: Analysis; Analytical Chemistry; Biological and medical sciences; Chemistry; Chemistry and Materials Science; Chromatography; Full Short Communication; General pharmacology; Laboratory Medicine; Medical sciences; Pharmacology. Drug treatments; Pharmacy; Proteomics; mPEG-glyceryl distearate micelles; Pharmacokinetic study; UPLC/MS/MS; Doxorubicin; Methanol precipitation–ultrasonic emulsion breaking method; Antineoplastic agent; Ultra performance liquid chromatography; Biological fluid; Tandem mass spectrometry; Chemical analysis; Intravenous administration; Rat; Diacylglycerol; Micelle; Electrospray; Blood; Blood plasma; Ethylene oxide polymer; Isomerases; Ultrasound; Quantitative analysis; Methanol; DNA topoisomerase (ATP-hydrolysing); Chemical precipitation; Enzyme; Coupled method; Multiple reaction monitoring mode; Rodentia; Enzyme inhibitor; Topoisomerase II inhibitor; Glyceride; Operating conditions; Vertebrata; Antibiotic; Mammalia; Animal; Methanol precipitation-ultrasonic emulsion breaking method; Anthracyclins; Antibacterial agent; Conjugated compound; Pharmacokinetics
• ISSN: 0009-5893; 1612-1112
• DOI: 10.1007/s10337-011-2066-7

This study established a new methanol precipitation–ultrasonic emulsion breaking method for extraction of doxorubicin from polymeric micelles and developed a UPLC–MS/MS method for the determination of doxorubicin in rat plasma. The emulsion breaking efficiency of methanol is up to 99.2%. The plasma samples were analyzed by UPLC/MS/MS using positive electrospray ionization mode in the multiple-reaction monitoring (MRM) mode. The calibration curves were linear over the range 5–1,000 ng mL
−1
with the lower limit of quantification of 5 ng mL
−1
. The intra- and inter-day precisions of QC samples were all <10.0%. The chromatographic separation was 2.5 min. The developed method was successfully applied to a pharmacokinetic study of doxorubicin in rats following intravenous administration.