title: Evaluation of a four-channel multiplexed electrospray triple quadrupole mass spectrometer for the simultaneous validation of LC/MS/MS methods in four different preclinical matrixes.
abstract: A four-channel multiplexed electrospray interface on a triple quadrupole mass spectrometer was evaluated for the simultaneous validation of LC/MS/MS methods for the quantitation of loratadine and its metabolite, descarboethoxyloratadine, in four different biological matrixes. The assays were performed in rat, rabbit, mouse, and dog plasma from 1 to 1000 ng/mL using 96-well solid-phase extraction for sample preparation. The limit of quantitation of 1 ng/mL corresponded to 5.56 pg of each analyte injected on-column. For the drug, quality control samples (n = 6 at four concentrations) had precision ranging from 0.967 to 16.0% and accuracy ranging from -8.44 to 10.5% across all four species. For the metabolite, the precision ranged from 0.684 to 11.0% and the accuracy was between 6.36 and -9.06%. Intersprayer cross talk for the multiplexed electrospray ion source was evaluated as a function of analyte concentration and was less than 0.08% at concentrations as high as 1000 ng/mL. These results demonstrate the feasibility of using parallel analysis to reduce the time required for method validation and to increase sample throughput in drug development studies.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033-1300, USA.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: T D
authors.initials: TD
authors.lastname: Mann
authors.forename: D
authors.initials: D
authors.lastname: Little
authors.forename: N
authors.initials: N
authors.lastname: Wu
authors.forename: R P
authors.initials: RP
authors.lastname: Clement
authors.forename: P J
authors.initials: PJ
authors.lastname: Rudewicz
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006634:Histamine H1 Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D007202:Indicators and Reagents; D017336:Loratadine / Q000097:blood* / Q000493:pharmacokinetics; D051379:Mice; D011817:Rabbits; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D006634:Histamine H1 Antagonists; D007202:Indicators and Reagents; D017336:Loratadine