Application of a liquid chromatography-electrospray mass spectrometry (LC/MS) method to the biodistribution and excretion studies of novel 5 '-chloro-2, 3-didehydroindolo (2 ', 3 ': 2, 3) betulinic acid (DRF-4012) in tumour-bearing mice

作者：Mishra Gautam^*; Singh Manoj Kumar; Awasthi Anshumali; Singh Anu T; Jaggi Manu; Ahmad Farhan J

来源：Xenobiotica, 2013, 43(6): 548-560.

DOI：10.3109/00498254.2012.747709

• LC/MS
• biodistribution study
• excretion study
• DRF-4012
• liquid-liquid extraction

Novel betulinic acid derivative 5'-chloro-2,3-didehydroindolo [2', 3': 2, 3] betulinic acid (DRF-4012) is a new effective lupane type triterpenes with greater anticancer activity and efficacy than betulinic acid and currently under advanced preclinical investigation phase. In this study, a sensitive and rapid liquid chromatography-electrospray mass spectrometric (LC/MS) method has been developed for the determination of DRF-4012 in tumour-bearing mice plasma, urine, feces and tissues (liver, brain, lungs, heart, spleen, stomach, thigh muscle, kidneys, urinary bladder, small intestine and tumour). Biodistribution and excretion studies were performed for DRF-4012 nanoparticle (30 mg/kg body weight) after intravenous (i. v.) injection in tumour-bearing mice. DRF-4012 rapidly distributed throughout the body. After 0.5 h, tumour showed the second highest concentration, which was nearly half of the liver. After 4 and 24 h, the highest concentration of DRF-4012 was found in tumour indicating its retention in tumour site for a longer time. Excretion studies revealed that very low amount of unchanged DRF-4012 was observed in urine and primarily excreted through fecal route. This study may be useful to explain the manner in which DRF-4012 can inhibit tumour growth without apparent toxicity and preclinical/clinical evaluation of this potential antitumour agent.

• 出版日期2013-6