title: 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.
abstract: 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.
authors.affiliation: Analytical -II & Drug Metabolism Laboratory, Dabur Research Foundation, Ghaziabad, India. gautam.mishra@daburresearch.in
authors.forename: Gautam
authors.initials: G
authors.lastname: Mishra
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Singh
authors.forename: Anshumali
authors.initials: A
authors.lastname: Awasthi
authors.forename: Anu T
authors.initials: AT
authors.lastname: Singh
authors.forename: Manu
authors.initials: M
authors.lastname: Jaggi
authors.forename: Farhan J
authors.initials: FJ
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D002138:Calibration; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D007211:Indoles / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D053978:Pentacyclic Triterpenes; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014018:Tissue Distribution; D014315:Triterpenes / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays; D000094062:Betulinic Acid
chemical_list: C587904:5'-chloro-2,3-didehydroindolo(2',3'-2,3)betulinic acid; D007211:Indoles; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid