title: Demonstration of the capabilities of a parallel high performance liquid chromatography tandem mass spectrometry system for use in the analysis of drug discovery plasma samples.
abstract: There is a continuing need for increased throughput in the evaluation of new drug entities in terms of their pharmacokinetic (PK) parameters. This report describes an alternative procedure for increasing the throughput of plasma samples assayed in one overnight analysis: the use of parallel high performance liquid chromatography (HPLC) combined with tandem mass spectrometry (parallel LC/MS/MS). For this work, two HPLC systems were linked so that their combined effluent flowed into one tandem MS system. The parallel HPLC/APCI-MS/MS system consisted of two Waters 2690 Alliance systems (each one included an HPLC pump and an autosampler) and one Finnigan TSQ 7000 triple quadrupole mass spectrometer. Therefore, the simultaneous chromatographic separation of the plasma samples was carried out in parallel on two HPLC systems. The MS data system was able to deconvolute the data to calculate the results for the samples. Using this system, 20 compounds were tested in one overnight assay using the rapid rat PK screening model which includes a total of 10 standards plus samples and two solvent blanks per compound tested. This application provides an additional means of increasing throughput in the drug discovery PK assay arena; using this approach a two-fold increase in throughput can be achieved in the assay part of the drug discovery rat PK screening step.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. walter.korfmacher@spcorp.com
authors.forename: W A
authors.initials: WA
authors.lastname: Korfmacher
authors.forename: J
authors.initials: J
authors.lastname: Veals
authors.forename: K
authors.initials: K
authors.lastname: Dunn-Meynell
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Tucker
authors.forename: K A
authors.initials: KA
authors.lastname: Cox
authors.forename: C C
authors.initials: CC
authors.lastname: Lin
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015507:Drugs, Investigational / Q000032:analysis* / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015507:Drugs, Investigational