Liquid Chromatography-Tandem Mass Spectrometry for the Simultaneous Determination of Doxorubicin and its Metabolites Doxorubicinol, Doxorubicinone, Doxorubicinolone, and 7-Deoxydoxorubicinone in Mouse Plasma

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 5; p. 1254
• Main Authors: Choi, Won-Gu, Kim, Dong Kyun, Shin, Yongho, Park, Ria, Cho, Yong-Yeon, Lee, Joo Young, Kang, Han Chang, Lee, Hye Suk
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.03.2020; MDPI
• Subjects: 7-deoxydoxorubicinone; Acids; Animals; Anthracycline; Antibiotics; Antibiotics, Antineoplastic - blood; Antibiotics, Antineoplastic - metabolism; Chloroform; Chromatography; Chromatography, Liquid - methods; Deoxyribonucleic acid; DNA; Doxorubicin; Doxorubicin - analogs & derivatives; Doxorubicin - blood; Doxorubicin - metabolism; doxorubicinol; doxorubicinolone; doxorubicinone; Drug dosages; Female; Intravenous administration; Ions; lc-ms/ms; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Metabolites; Methods; Mice; Mice, Inbred BALB C; Mice, Nude; mouse plasma; Naphthacenes - blood; Pharmacokinetics; Plasma; Plasma - metabolism; Quality control; Scientific imaging; Spectroscopy; Tandem Mass Spectrometry - methods; United States > US; LC-MS/MS; doxorubicinol; 7-deoxydoxorubicinone; doxorubicinone; mouse plasma; doxorubicinolone; doxorubicin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25051254

Doxorubicin, an anthracycline antitumor antibiotic, acts as a cancer treatment by interfering with the function of DNA. Herein, liquid chromatography-tandem mass spectrometry was for the first time developed and validated for the simultaneous determination of doxorubicin and its major metabolites doxorubicinol, doxorubicinone, doxorubicinolone, and 7-deoxydoxorubicinone in mouse plasma. The liquid-liquid extraction of a 10 μL mouse plasma sample with chloroform:methanol (4:1, / ) and use of the selected reaction monitoring mode led to less matrix effect and better sensitivity. The lower limits of quantification levels were 0.5 ng/mL for doxorubicin, 0.1 ng/mL for doxorubicinol, and 0.01 ng/mL for doxorubicinone, doxorubicinolone, and 7-deoxydoxorubicinone. The standard curves were linear over the range of 0.5-200 ng/mL for doxorubicin; 0.1-200 ng/mL for doxorubicinol; and 0.01-50 ng/mL for doxorubicinone, doxorubicinolone, and 7-deoxydoxorubicinone in mouse plasma. The intra and inter-day relative standard deviation and relative errors for doxorubicin and its four metabolites at four quality control concentrations were 0.9-13.6% and -13.0% to 14.9%, respectively. This method was successfully applied to the pharmacokinetic study of doxorubicin and its metabolites after intravenous administration of doxorubicin at a dose of 1.3 mg/kg to female BALB/c nude mice.