title: Direct injection of whole blood for liquid chromatography/tandem mass spectrometry analysis to support single-rodent pharmacokinetic studies.
abstract: Mass spectrometric developments in the last decade enable (sub)nanomolar detection of drug compounds in biological matrices in a few microliters of blood. However, the sampling and especially the handling of these small blood volumes is not straightforward. We studied the feasibility of a recently developed 'sorbent sampling technique' to handle these small blood volumes and the application to support pharmacokinetic (PK) screening programs. This technique applies 5-10 microL of blood on a fibrous material packed into a cartridge. Blood samples absorbed on these cartridges are eluted directly, on-line onto a solid-phase extraction liquid chromatography/tandem mass spectrometry (SPE-LC/MS/MS) system. It is shown that the sorbent sampling technique can be applied for a range of drug compounds. In spite of issues with recovery and sample clean-up that need further improvement, the sorbent sampling technique provided similar data as compared to conventional analytics. The technique was successfully applied to derive kinetic data from individual mice, thereby decreasing the number of required mice for a PK study from 21 to 3.
authors.affiliation: N.V. Organon, a part of Schering-Plough Corporation, Molenstraat 110, P.O. Box 20, 5340 BH Oss, The Netherlands. benno.ingelse@organon.com
authors.forename: Benno A
authors.initials: BA
authors.lastname: Ingelse
authors.forename: Gerard
authors.initials: G
authors.lastname: Vogel
authors.forename: Margriet
authors.initials: M
authors.lastname: Botterblom
authors.forename: Dennis
authors.initials: D
authors.lastname: Nanninga
authors.forename: Bert
authors.initials: B
authors.lastname: Ooms
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis / Q000295:instrumentation / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D017022:Flow Injection Analysis / Q000295:instrumentation / Q000379:methods*; D007267:Injections; D051379:Mice; D008807:Mice, Inbred BALB C; D004364:Pharmaceutical Preparations / Q000097:blood*; D010599:Pharmacokinetics; D013048:Specimen Handling / Q000295:instrumentation / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations