title: Using Visualized Matrix Effects to Develop and Improve LC-MS/MS Bioanalytical Methods, Taking TRAM-34 as an Example.
abstract: Matrix effects (MEs) continue to be an obstacle in the development of the LC-MS/MS method, with phospholipids being the major cause of MEs. Changing the mobile phase has been a common strategy to reduce MEs; however, the underlying mechanism is unclear. "In-source multiple-reaction monitoring" (IS-MRM) for glycerophosphocholines (PCs) has been commonly applied in many bioanalytical methods. "Visualized MEs" is a suitable term to describe the application of IS-MRM to visualize the elution pattern of phospholipids. We selected a real case to discuss the relationship of MEs and phospholipids in different mobile phases by quantitative, qualitative, and visualized MEs in LC-MS/MS bioanalysis. The application of visualized MEs not only predicts the ion-suppression zone but also helps in selecting an appropriate (1) mobile phase, (2) column, (3) needle wash solvent for the residue of analyte and phospholipids, and (4) evaluates the clean-up efficiency of sample preparation. The TRAM-34 LC-MS/MS method, improved by using visualized MEs, was shown to be a precise and accurate analytical method. All data indicated that the use of visualized MEs indeed provided useful information about the LC-MS/MS method development and improvement. In this study, an integrative approach for the qualitative, quantitative, and visualized MEs was used to decipher the complexity of MEs.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Jia-Hung
authors.initials: JH
authors.lastname: Ye
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan, Republic of China; Graduate Institute of Health-Industry Technology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan, Republic of China.
authors.forename: Li-Heng
authors.initials: LH
authors.lastname: Pao
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D008297:Male; D010743:Phospholipids / Q000737:chemistry; D010949:Plasma / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry*; D051381:Rats; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010743:Phospholipids; D011720:Pyrazoles; C411671:TRAM 34