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

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 tum...