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

被引:69
作者
Yang, LY
Mann, TD
Little, D
Wu, N
Clement, RP
Rudewicz, PJ
机构
[1] Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA
[2] Micromass Inc, Beverly, MA 01915 USA
[3] Micromass UK Ltd, Manchester M23 9LZ, Lancs, England
关键词
D O I
10.1021/ac0012694
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
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.
引用
收藏
页码:1740 / 1747
页数:8
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