APPLICATION OF DBS METHODOLOGY FOR A COMPARATIVE ASSESSMENT OF PHENYTOIN IN DBS AND PLASMA SAMPLES OF A PHARMACOKINETIC RAT STUDY USING LC–MS/MS METHOD

Vijay Kumar Raina; Wishu Shrivastava; Akena Venkatesham; Yuan Song; P.K. Patel

Volume : IV, Issue : V, May - 2015

APPLICATION OF DBS METHODOLOGY FOR A COMPARATIVE ASSESSMENT OF PHENYTOIN IN DBS AND PLASMA SAMPLES OF A PHARMACOKINETIC RAT STUDY USING LC–MS/MS METHOD

Vijay Kumar Raina, Wishu Shrivastava, Akena Venkatesham, Yuan Song, P. K. Patel

Abstract :

DBSis a less invasive microsamplingtechniquewhich offers ethical and logistical benefits overconventional blood sampling technique. Due to dry format nature of these samples, there is also a reduced risk of pathogen infectionwhile handling samples. The techniquehas been traditionally used asa screening tool in biomedical testing but recently itsutility is emergingin drug development particularly in pharmacokinetic (PK), toxicokinetic (TK), and therapeutic drug monitoring (TDM) studies. Bioanalysis is the key element of drug development that enables accurate quantitation of drug concentrations in study samples. But DBS bioanalysis,unlike conventionalplasma bioanalysis, isrelatively new and quite challenging neverthelessevolving.This research work describes the application of DBS bioanalysis to measure concentrations of a therapeutic drug in rat PK samplesand to draw a correlation with plasma bioanalysis. A novel and sensitive DBS–LC–MS/MS bioanalytical method for Phenytoin was developed and validated for sensitivity, precision, accuracy, stability and recovery to analyse DBS and plasma samples of a rat PK study. The observed mean PK profile of DBS and plasmademonstrated a good correlation supporting the rationaleto apply theDBS methodtoPhenytoin and similar therapeutic drugs