title: Highly sensitive method for the determination of a novel triple kinase inhibitor with anti-cancer activity, JI-101, in rat plasma by liquid chromatography-electrospray ionization tandem mass spectrometry: application to a pharmacokinetic study.
abstract: A highly sensitive, rapid assay method has been developed and validated for the estimation of JI-101 in rat plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The assay procedure involves extraction of JI-101 and phenacetin (internal standard, IS) from rat plasma with a solid-phase extraction process. Chromatographic separation was achieved using a binary gradient using mobile phase A (acetonitrile) and B (0.2% formic acid in water) at a flow rate of 0.30 mL/min on a Prodigy ODS column with a total run time of 4.0 min. The MS/MS ion transitions monitored were 466.1 → 265 for JI-101 and 180.1 → 110.1 for IS. Method validation and sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 5.03 ng/mL and the linearity range extended from 5.03 to 2014 ng/mL. The intra-day and inter-day precisions were in the ranges of 1.17-19.6 and 3.09-10.4%, respectively. This method has been applied to a pharmacokinetic study of JI-101 in rats.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Industrial Suburb, Yeshwanthpur, Bangalore-560022, India.
authors.forename: Sandip Dhondiram
authors.initials: SD
authors.lastname: Gurav
authors.forename: Ravindranath Reddy
authors.initials: RR
authors.lastname: Gilibili
authors.forename: Sherine
authors.initials: S
authors.lastname: Jeniffer
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Giri
authors.forename: Nuggehally R
authors.initials: NR
authors.lastname: Srinivas
authors.forename: Ramesh
authors.initials: R
authors.lastname: Mullangi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D007211:Indoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D010671:Phenylurea Compounds / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C561574:1-(1-(2-amino-pyridin-4-ylmethyl)-1H-indol-4-yl)-3-(5-bromo-2-methoxyphenyl)urea; D000970:Antineoplastic Agents; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors