Determination of androgen receptor degradation enhancer ASC-J9 (R) in mouse sera and organs with liquid chromatography tandem mass spectrometry

作者：Soh Shu Fang; Huang Chiung Kuei; Lee Soo Ok; Xu Defeng; Yeh Shuyuan; Li Jun; Yong Eu Leong; Gong Yinhan^*; Chang Chawnshang

来源：Journal of Pharmaceutical and Biomedical Analysis, 2014, 88: 117-122.

DOI：10.1016/j.jpba.2013.08.020

• ASC-J9 (R)
• Androgen receptor
• Liquid chromatography tandem mass spectrometry Pharmacokinetics
• Distribution of drug

A novel androgen receptor (AR) degradation enhancer ASC-J9 (R) 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 (R) in 100 mu L of mouse serum by using liquid chromatography tandem mass spectrometry (LC-MS/MS). The limit of quantification (LOQ) was found to be 5 nM for ASCJ9 (R). This method was successfully applied to investigate the pharmacokinetics of ASC-J9 (R) 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 (R) could be quickly absorbed in vivo and had a relatively slow elimination half-life of 5.45 h. The ASC-J9 (R) also exhibited a higher tendency to accumulate in organs such as liver, testes and prostate.

• 出版日期2014-1-25
• 单位中国医科大学