RESUMO
Prostate cancer (PCa) is the most commonly diagnosed cancer in men worldwide. It is essentially dependent on potent androgens, such as testosterone (T) and dihydrotestosterone (DHT). The precursors of T and DHT, which includes androstenedione (A4) and dihydroepiandrosterone (DHEA), and also the metabolites of DHT, 5α-androstane-3α,17ß-diol (3α-Diol) and 5α-androstane-3ß,17ß-diol (3ß-Diol) are able to affect the development of PCa. Therefore, it is important to simultaneously determine all these key androgens. This study aims to develop and validate an LC-MS/MS quantification method to simultaneously detect and quantify the six related androgens, including T, DHT, A4, DHEA, 3α-Diol, and 3ß-Diol in limited sample volume. The sample preparation involved liquid extraction with methyl tert-butyl ether (MTBE), following by chemical derivatisation with hydroxylamine. The limits of quantitation for T, DHT, A4, and DHEA were 0.05nM and 3α-Diol and 3ß-Diol were 0.5nM with S/N ratio of at least 5:1 by using 100µL samples.
Assuntos
Androgênios/metabolismo , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem , Animais , Antineoplásicos/administração & dosagem , Curcumina/administração & dosagem , Curcumina/análogos & derivados , Hidroxilamina/química , Extração Líquido-Líquido , Masculino , Éteres Metílicos/química , Camundongos Endogâmicos C57BL , Reprodutibilidade dos TestesRESUMO
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.
Assuntos
Curcumina/análogos & derivados , Receptores Androgênicos/análise , Androgênios/química , Animais , Calibragem , Proliferação de Células , Cromatografia Líquida , Curcumina/química , Curcumina/farmacocinética , Meia-Vida , Limite de Detecção , Modelos Lineares , Fígado/efeitos dos fármacos , Masculino , Camundongos , Próstata/efeitos dos fármacos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Testículo/efeitos dos fármacos , Distribuição TecidualRESUMO
Two new types of methylcalix[4]resorcinarene-bonded stationary phases, (3-(C-methylcalix[4]resorcinarene)-2-hydroxypropoxy)-propylsilyl-appended silica particles (MCR-HPS) and bromoacetate-substituted MCR-HPS particles (BAMCR-HPS), have been synthesized and used as chiral stationary phases for high-performance liquid chromatography (HPLC) for the first time. The synthetic stationary phases are characterized by means of elemental analysis and Fourier-transform infrared spectroscopy. The chromatographic behavior of MCR-HPS and BAMCR-HPS was studied with several disubstituted benzenes and some chiral drug compounds under both normal phase and reversed-phase conditions. The results show that MCR-HPS has excellent selectivity for the separation of aromatic positional isomers and BAMCR-HPS exhibits excellent performance for separation of enantiomers of chiral compounds.
