Journal des techniques analytiques et bioanalytiques

Abstrait

Identification and Reduction of Matrix Effects Caused by Solutol Hs15 in Bioanalysis Using Liquid Chromatography/Tandem Mass Spectrometry

Vijaya Bhaskar V, Anil Middha, Sudhir Tiwari and Savithiri Shivakumar

Ion suppression effect of dosing vehicle excipient Solutol HS15 (SHS15) on the accuracy of liquid chromatography/ tandem mass spectrometry (LC-MS/MS) measurements was studied. Ion supression cause significant errors in accuracy of the measured concentrations of test compounds, thereby invalidating the assessment of pharmacokinetic results. Using SHS15 as a probe compound, the concentration-time profile of the excipient in plasma from rats dosed both orally and intravenously was determined. A total of twelve oligomers were identified for SHS15. The most abundant ions corresponding to SHS15 oligomers at m/z 481, 525, 569, 613, 657, 701, 745, 789, 833, 877, 921, 965 were selected for pseudomultiple reaction monitoring (pMRM) in electrospray mode of ionisation. Analyte peak area of the oligomers was summed up to calculate the plasma concentrations of total SHS15. Plasma concentrations of SHS15 ranging from 1-2 mg/mL in the initial sampling points caused 2-10 fold ion supression on most of the analytes studied. This can result in false rejection of compounds in a drug discovery screen. Several sample preparation methods, enhanced chromatographic selectivity, and alternative ionization methods were investigated as means to avoid or minimize ion suppression effects. The elimination of ion suppression effects was achieved by liquid liquid extraction (LLE) with hexane, tert-butyl-methyl ether (TBME) as sample preparation method. The mechanism of ion supression caused by SHS15 in relation to both liquid and gas phase reactions was proposed.