title: Quantitative determination of intracellular Asulacrine in MCF-7 breast cancer cells by liquid chromatography-mass spectrometry and its application to cellular pharmacokinetic studies of P188 modified liposomes.
abstract: Asulacrine (ASL), an analogue of amsacrine, has shown higher anti-breast and anti-lung cancer activity. Hereby, a new sensitive and selective liquid chromatography-mass spectrometry (LC/MS) method was developed to determine intracellular asulacrine. The chromatographic separation was performed on an Agilent Zorbax Extend-C18column (2.1 mm i.d. × 50 mm, 5 μm) using gradient elution with water (2 mmol/L ammonium acetate and 0.1% acetic acid) and acetonitrile as the mobile phase. The detection was achieved with selected ion monitoring mode using electrospray ionization in positive mode with target ions at m/z 465.3 and m/z 326.1 for asulacrine and midazolam, respectively. The standard curve showed a good linearity with the lower limit of quantification of 1 ng/mL, as a result of which, the trace concentration of ASL in cell suspension could be quantified. The intra- and inter-day accuracy ranged from -5.28 to 6.5% and from -6.32 to 1.05%, and the intra- and inter-day precisions were no more than 7.65% and 11.71%, respectively. Additionally, no degradation of asulacrine was observed during stability evaluation. The method was proved to be powerful and practical to determine and compare the intracellular distribution and kinetics of ASL under different formulations in MCF-7 breast cancer cells.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Zang
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Qianying
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Sun
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Liu
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
mesh_terms: D000677:Amsacrine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D008081:Liposomes; D061986:MCF-7 Cells; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D000677:Amsacrine; C042315:asulacrine
keywords: LC/MS; asulacrine; intracellular concentration; liposome