Expanding the linear dynamic range in quantitative high performance liquid chromatography/tandem mass spectrometry by the use of multiple product ions

Abstract

A strategy for expanding the linear working range in bioanalysis using quantitative high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) is presented. The strategy involves monitoring multiple product ions. Herein we demonstrate the strategy on a rat plasma assay for a proprietary experimental drug where the linear range is expanded from 2 to 4 orders of magnitude. A primary sensitive ion was monitored to obtain a high sensitivity range calibration curve (0.400 to 100 ng/mL) while a less sensitive secondary ion was monitored to obtain a low sensitivity range calibration curve (90.0 to 4000 ng/mL). Each calibration curve gave acceptable linearity (r >0.990). Quality control samples at low, mid and high levels within each calibration curve demonstrated acceptable precision and accuracy (within 20% for all levels). The technique was successfully applied to rat pre-clinical sample analysis.

Enantioselective Reduction of α‐Cyano and α‐Nitro Substituted Acetophenones Promoted by a Bifunctional Mesoporous Silica

“…This paper describes a methodology to extend the linear dynamic range of a triple quadrupole mass spectrometer without the need for pre‐ or post‐analysis dilution schemes. Similar approaches have been reported, where the linear dynamic range was expanded through the use of simultaneous acquisition of different mass transitions for a single analyte 2. Our work demonstrates the ability to create a selected reaction monitoring (SRM) method that simultaneously collects data for the same mass transition with variable and tunable sensitivity, achieved via collision energy (CE) adjustment.…”

Expanding the Versatility of a Quantitative Determination Range Adjustment Technique Using In-Source CID in LC/MS/MS

“…In addition, we succeeded in applying the technique to the quantification of a drug and its metabolites, which had different sensitivities on ESI-MS/MS, in a complex biological fluid [5]. Although two useful techniques, monitoring isotopologue transitions in selected reaction monitoring mode (i-SRM) [6,7] and monitoring secondary product ions in SRM mode (s-SRM) [8,9] have already been developed for the same purpose by limiting ion amounts into electron multiplier, our technique using in-source CID was more effective for improvement of linearity because of controlling ion amounts at the ion inlet of orifice to widen the linear quantification range [4]. Therefore, the linear range shifting technique using in-source CID would provide a versatile system for bioanalysis if it exhibits similar effects under other…”

Increasing the linear dynamic range in LC–MS: is it valid to use a less abundant isotopologue?

“…In modern LC-MS instruments, the reason for non-linearity at higher concentrations is often due to detector saturation. [4][5][6][7] For methods targeting selected compounds using triple quadrupole (QQQ) tandem mass spectrometry (MS/MS), this problem may be somewhat overcome by altering MS parameters for each compound to intentionally reduce sensitivity; or by using both high and low sensitivity transitions [7,8] or detection polarities [9,10] for different calibration ranges or compounds.…”