阿霉素
化学
色谱法
药代动力学
液相色谱-质谱法
蒽环类
代谢物
串联质谱法
质谱法
检出限
药理学
癌症
生物化学
医学
化疗
内科学
乳腺癌
作者
Won-Gu Choi,Dong Kyun Kim,Yongho Shin,Ria Park,Yong‐Yeon Cho,Joo Young Lee,Han Chang Kang,Hye Suk Lee
出处
期刊:Molecules
[MDPI AG]
日期:2020-03-10
卷期号:25 (5): 1254-1254
被引量:8
标识
DOI:10.3390/molecules25051254
摘要
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, v/v) 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.
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