ABSTRACT
Aim To investigate the intracellular disposition process of doxorubicin (DOX) in human breast cancer MCF-7, providing reference for explaining the pharmacology and their side effects of anti-tumor drugs. Methods The drug-resistant cell line MCF-7/DOX of breast cancer with DOX indication was selected as the material, and ultra-high performance liquid chromatography quadrupole tandem time-of-flight high-resolution mass spectrometry (UPLC-Q-TOF-MS/MS) method was established to analyze the disposal of DOX by target cells. Results Two unreported trace a-mounts of new metabolites of doxorubicin were found, and their structures were deduced by high-resolution multistage mass spectrometry. Molecular docking showed that its affinity for DNA was lower than that of DOX. Conclusion Target cells have unique and diverse drug metabolism pathways for DOX, which may be related to drug resistance mechanisms.
ABSTRACT
Objective To develop an ultra-performance liquid chromatography/quadrupole-time of flight mass spectrometry(UPLC-QTOF-MS)method for the determination of an oxadiazole-2-oxide heterocyclic compound F-2015-14.Methods Mouse plasma and liver homogenate specimens were extracted with ethyl acetate and chromatographed on a Waters CORTECS column(C18,1.6μm,2.1 mm×150 mm)by using a mobile phase of 10％acetonitrile-0.1％formic acid with by a volume fractionation by gradient elution.Then,UPLC-QTOF-MS was performed to determine F-2015-14 in mouse plasma and liver homogenate speci-mens.Results The linearity of F-2015-14 in plasma ranged from 12.5 to 250 μg/mL with a correlation coefficient of 0.990 and a detection limit of 8.8 μg/mL.F-2015-14 in liver homogenates ranged from 12.5 to 250 μg/mL.The linearity was good with a cor-relation coefficient of 0.992 and a limit of detection of 5.6 μg/mL.If the concentration of plasma and liver homogenate specimens was 12.5 μg/mL,the accuracy and the matrix effect were 80％to 120％,and the inter-day and intra-day precision was within 20％.If the concentrations of plasma and liver homogenate specimens were 100 μg/mL and 200 μg/mL,the accuracy and the ma-trix effect were 85％to 115％,and the inter-day and intra-day precision was within 15％.Conclusion The UPLC-QTOF-MS es-tablished in this study has a high sensitivity and good reproducibility for the determination of F-2015-14,which provides bases for the development of novel anti-schistosomiasis drugs.