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.

Multiplex multidimensional nanoLC-MS system for targeted proteomic analyses

“…The MS signals from individual electrospray stream are acquired in separate acquisition channels [29]. However, the sensitivity of the multiplex system was reported to be approximately three times lower than that the conventional single sprayer interface [30]. Other reports have presented staggered nanoLC column arrangements for proteomics applications where serially connected dual-capillary column devices were used in turn to reduce time delays for column regeneration and analysis since one-capillary column was used for a separation while the other was being washed [31].…”

Pulsed dual electrospray ionization for In/In reactions

“…In the other typical operation mode, ions from distinct sprayers can be sampled sequentially by utilizing a rotatable plate [42] or rotor [43], which allow ions from a specific sprayer to enter the mass spectrometer sequentially. The mechanical switching may decrease the overall MS duty cycle and decrease sensitivity when compared to that of a single sprayer [44]. Other techniques have also been used for sequential sampling of ions, such as the application of an appropriate potential to an atmospheric pressure ion lens [36] and the alternate switching of voltages applied to the sprayers from a low potential to a high potential [40].…”

The Expanding Role of HPLC in Drug Discovery

“…Yang et al [98] identified the two main advantages of parallel LC-MS/MS using Micromass Ultima with MUX interface to be (a) parallel analysis and (b) four times the throughput relative to single-column systems. However, disadvantages were reported as (a) cross-talk between the sprayers (negligible at concentrations <100 ng/mL but as high as 0.08% at 1000 ng/mL), (b) sensitivity less than that of a single sprayer interface (about 3 × lower than the single sprayer interface), and (c) total cycle time longer than that of a single sprayer interface (hence not compatible with ultrafast chromatography).…”