Katja Heinig1, Thomas Wirz, Franz Bucheli, Almudena Gajate-Perez. 1. F. Hoffmann-La Roche AG, Pharma Research, Nonclinical Drug Safety, Development DMPK Department, Grenzacherstrasse 124, 4070 Basel, Switzerland. katja.heinig@roche.com
Abstract
BACKGROUND: Using dried blood spots (DBS) for quantitation of the antiviral drug oseltamivir (Tamiflu(®)), an ester prodrug, and its active metabolite oseltamivir carboxylate could provide ethical and logistic benefits. Hence, its feasibility was investigated using a previously developed column-switching LC-MS/MS method. RESULTS: Sensitivity, precision and accuracy in DBS were comparable to standard plasma assays. Chemically treated cards provided enhanced ex vivo stability of the ester prodrug in rodent blood. Online extraction was realized using the manual TLC-MS interface or the fully automated Sample Card and Prep system. Rat pharmacokinetic study data showed good correlation between plasma, liquid blood and DBS. CONCLUSION: From a bioanalytical perspective, DBS is potentially suited for Tamiflu analysis in animals and humans. Automation of the process by online DBS extraction promises workload reduction and throughput increase.
BACKGROUND: Using dried blood spots (DBS) for quantitation of the antiviral drug oseltamivir (Tamiflu(®)), an ester prodrug, and its active metabolite oseltamivir carboxylate could provide ethical and logistic benefits. Hence, its feasibility was investigated using a previously developed column-switching LC-MS/MS method. RESULTS: Sensitivity, precision and accuracy in DBS were comparable to standard plasma assays. Chemically treated cards provided enhanced ex vivo stability of the ester prodrug in rodent blood. Online extraction was realized using the manual TLC-MS interface or the fully automated Sample Card and Prep system. Rat pharmacokinetic study data showed good correlation between plasma, liquid blood and DBS. CONCLUSION: From a bioanalytical perspective, DBS is potentially suited for Tamiflu analysis in animals and humans. Automation of the process by online DBS extraction promises workload reduction and throughput increase.
Authors: Gero P Hooff; Roland J W Meesters; Jeroen J A van Kampen; Nick A van Huizen; Birgit Koch; Asmar F Y Al Hadithy; Teun van Gelder; Albert D M E Osterhaus; Rob A Gruters; Theo M Luider Journal: Anal Bioanal Chem Date: 2011-05-03 Impact factor: 4.142