title: Determination of androgen receptor degradation enhancer ASC-J9(®) in mouse sera and organs with liquid chromatography tandem mass spectrometry.
abstract: A novel androgen receptor (AR) degradation enhancer ASC-J9(®) has displayed beneficial effects during the in vitro and in vivo studies for treatment of prostate cancer, liver cancer, bladder cancer and spinal and bulbar muscular atrophy (SBMA). It works mainly via the degradation of AR with minimal side effects on the tested mice. Here we developed a fast, robust and more sensitive method for the quantification of ASC-J9(®) in 100μL of mouse serum by using liquid chromatography tandem mass spectrometry (LC-MS/MS). The limit of quantification (LOQ) was found to be 5nM for ASCJ9(®). This method was successfully applied to investigate the pharmacokinetics of ASC-J9(®) in mice serum samples and also the distribution of the drug in various mice organs after single dose injection with results showing that ASC-J9(®) could be quickly absorbed in vivo and had a relatively slow elimination half-life of 5.45h. The ASC-J9(®) also exhibited a higher tendency to accumulate in organs such as liver, testes and prostate.
authors.affiliation: Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074; George Whipple Lab for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Shu Fang
authors.initials: SF
authors.lastname: Soh
authors.forename: Chiung-Kuei
authors.initials: CK
authors.lastname: Huang
authors.forename: Soo Ok
authors.initials: SO
authors.lastname: Lee
authors.forename: Defeng
authors.initials: D
authors.lastname: Xu
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Eu Leong
authors.initials: EL
authors.lastname: Yong
authors.forename: Yinhan
authors.initials: Y
authors.lastname: Gong
authors.forename: Chawnshang
authors.initials: C
authors.lastname: Chang
mesh_terms: D000728:Androgens / Q000737:chemistry; D000818:Animals; D002138:Calibration; D049109:Cell Proliferation; D002853:Chromatography, Liquid; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D006207:Half-Life; D057230:Limit of Detection; D016014:Linear Models; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D011467:Prostate / Q000187:drug effects; D011944:Receptors, Androgen / Q000032:analysis*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D013737:Testis / Q000187:drug effects; D014018:Tissue Distribution
chemical_list: D000728:Androgens; D003474:Curcumin; D011944:Receptors, Androgen; C471106:ASC-J9 compound
keywords: ASC-J9(®); Androgen receptor; Distribution of drug; Liquid chromatography tandem mass spectrometry; Pharmacokinetics
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