title: Use of polarity switching for the simultaneous bioanalysis of analytes with three orders of magnitude difference in concentration by LC-MS/MS.
abstract: BACKGROUND
  The challenge of quantifying two compounds in a single assay with drastic dynamic ranges is to obtain linearity without source or detector saturation at the mass spectrometer.
  
  
  RESULTS
  In positive-ionization mode, the nonlinear relationships for Desmethyl Mebeverine Acid (DMAC) were demonstrated using three common strategies to overcome this issue: using offset voltage parameters, less-sensitive product ion or 13C mass SRM transitions. On the contrary, nonlinear relationships for DMAC were overcome if negative-ionization mode was used. Due to Mebeverine analytical LLOQ, dilution was not suitable for a single assay of Mebeverine and DMAC. However, polarity switching in negative mode for DMAC was successfully found to compensate for the nonlinearity at the mass spectrometer while preserving Mebeverine linear regression model in positive mode.
  
  
  CONCLUSIONS
  The polarity switching strategy has demonstrated the advantage of improving linearity for analytes having different ionization polarities and three orders of magnitude difference in concentration.
authors.affiliation: Algorithme Pharma Inc., 575 Armand-Frappier, Laval, QC H7V 4B3, Canada.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bergeron
authors.forename: Annik
authors.initials: A
authors.lastname: Bergeron
authors.forename: Peter
authors.initials: P
authors.lastname: van Amsterdam
authors.forename: Milton
authors.initials: M
authors.lastname: Furtado
authors.forename: Fabio
authors.initials: F
authors.lastname: Garofolo
mesh_terms: D000927:Anticonvulsants / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D015394:Molecular Structure; D017711:Nonlinear Dynamics; D010627:Phenethylamines / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D012015:Reference Standards; D012044:Regression Analysis; D012996:Solutions; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000927:Anticonvulsants; D010627:Phenethylamines; D012996:Solutions; C005096:mebeverine