1 research outputs found
Differential Mobility Spectrometry Coupled with Multiple Ion Monitoring in Regulated LC-MS/MS Bioanalysis of a Therapeutic Cyclic Peptide in Human Plasma
A differential
mobility spectrometry (DMS) in combination with
a multiple ion monitoring (MIM) method was developed and validated
for quantitative LC-MS/MS bioanalysis of pasireotide (SOM230) in human
plasma. Pasireotide, a therapeutic cyclic peptide, exhibits poor collision-induced
dissociation (CID) efficiency for multiple reaction monitoring (MRM)
detection. Therefore, in an effort to increase the overall sensitivity
of the assay, a DMS-MIM approach was explored. By selecting the most
abundant doubly charged precursor ion in both the Q1 and Q3 of the
mass analyzer in MIM and combining the DMS capability to significantly
reduce the high matrix/chemical background noise, this new LC-DMS-MIM
method overcomes the sensitivity challenge in the typical MRM method
due to poor CID fragmentation of the analyte. Human plasma was spiked
with pasireotide with concentrations in the range 0.01–50 ng/mL.
Weak cation-exchange solid-phase extraction was employed for sample
preparation. The sample extracts were analyzed with a SCIEX QTRAP
6500 system equipped with an ESI source and DMS device. The separation
voltage and compensation voltage of the DMS and other parameters of
the MS system were optimized to maximize signal responses. The performance
of the LC-DMS-MIM assay for quantitative analysis of pasireotide in
human plasma was evaluated and compared to those obtained via LC-MRM
and LC-MIM without DMS. Overall, the assay sensitivity with DMS-MIM
was approximately 5-fold better than that observed in MRM or MIM without
DMS. The assay was validated with accuracy (% bias) and precision
(% CV) of the QC results at eight concentration levels (0.01, 0.02,
0.05, 0.15, 0.3, 1.5, 15, and 37.5 ng/mL) evaluated ranging from −4.8
to 5.0% bias and 0.7 to 8.6% CV for the intraday and interday runs.
The current LC-DMS-MIM workflow can be expanded to quantitative analysis
of other molecules that have poor fragmentation efficiency in CID