title: A strategy for extending the applicability of a validated plasma calibration curve to quantitative measurements in multiple tissue homogenate samples: a case study from a rat tissue distribution study of JI-101, a triple kinase inhibitor.
abstract: A general practice in bioanalysis is that, whatever the biological matrix the analyte is being quantified in, the validation is performed in the same matrix as per regulatory guidelines. In this paper, we are presenting the applicability of a validated LC-MS/MS method in rat plasma for JI-101, to estimate the concentrations of JI-101 in various tissues that were harvested in a rat tissue distribution study. A simple protein precipitation technique was used to extract JI-101 and internal standard from the tissue homogenates. The recovery of JI-101 in all the matrices was found to be >70%. 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 internal standard. The linearity range was 5.02-4017 ng/mL. The JI-101 levels were quantifiable in the various tissue samples harvested in this study. Therefore, the use of a previously validated JI-101 assay in plasma circumvented the tedious process of method development/validation in various tissue matrices.
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: Sherine
authors.initials: S
authors.lastname: Jeniffer
authors.forename: Ravindra
authors.initials: R
authors.lastname: Punde
authors.forename: Ravindranath Reddy
authors.initials: RR
authors.lastname: Gilibili
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; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D007211:Indoles / Q000097:blood / Q000493:pharmacokinetics*; D016014:Linear Models; D008297:Male; D010671:Phenylurea Compounds / Q000097:blood / Q000493:pharmacokinetics*; D047428:Protein Kinase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: C561574:1-(1-(2-amino-pyridin-4-ylmethyl)-1H-indol-4-yl)-3-(5-bromo-2-methoxyphenyl)urea; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors