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. (June 2013)

• Record Type: Journal Article
• Authors: Mishra, Gautam; Singh, Manoj Kumar; Awasthi, Anshumali; Singh, Anu T.; Jaggi, Manu; Ahmad, Farhan J.
• Is Part Of: Xenobiotica. Volume 43:Number 6(2013:Jun.)
• Page Start: 548
• Page End: 560
• Publication Date: 2013-06
• Subjects: Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.3109/00498254.2012.747709
• Languages: English
• ISSNs: 0049-8254

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>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.</p> </abstract>