title: Impact of APCI ionization source in liquid chromatography tandem mass spectrometry based tissue distribution studies.
abstract: Measurement of test article concentration in tissue samples has been an important part of pharmacokinetic study and has helped to co-relate pharmacokinetic/pharmacodynamic relationships since the 1950s. Bioanalysis of tissue samples using LC-MS/MS comes with unique challenges in terms of sample handling and inconsistent analyte response owing to nonvolatile matrix components. Matrix effect is a phenomenon where the target analyte response is either suppressed or enhanced in the presence of matrix components. Based on previous reports electrospray ionization (ESI) mode of ionization is believed to be more affected by matrix components than atmospheric pressure chemical ionization (APCI) or atmospheric pressure photoionization. To explore the impact of ionization source with respect to bioanalysis of tissue samples, five structurally diverse compounds - atenolol, verapamil, diclofenac, propranolol and flufenamic acid - were selected. Quality control standards were spiked into 10 different biological matrices like whole blood, liver, heart, brain, spleen, kidney, skeletal muscle, eye and skin tissue and were quantified against calibration standards prepared in rat plasma. Quantitative bioanalysis was performed utilizing both APCI and ESI mode and results were compared. Quality control standards when analyzed with APCI mode were found to be more consistent in terms of accuracy and precision as compared with ESI mode. Additionally, for some instances, up to 20-fold broader dynamic linearity range was observed with APCI mode as compared with ESI mode. As phospholid interferences have poor response in APCI mode, protein precipitation extraction technique can be used for multimatrix quantitation, which is more amenable to automation. The approach of multiple biological matrix quantitation against a single calibration curve helps bioanalysts to reduce turnaround time. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Advinus Therapeutics Ltd, Pune, India.
authors.forename: Laxman
authors.initials: L
authors.lastname: Khatal
authors.affiliation: Advinus Therapeutics Ltd, Pune, India.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Gaur
authors.affiliation: Advinus Therapeutics Ltd, Pune, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Naphade
authors.affiliation: Advinus Therapeutics Ltd, Pune, India.
authors.forename: Vishwottam
authors.initials: V
authors.lastname: Kandikere
authors.affiliation: Advinus Therapeutics Ltd, Pune, India.
authors.forename: Kasim
authors.initials: K
authors.lastname: Mookhtiar
mesh_terms: D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D008297:Male; D011786:Quality Control; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
keywords: APCI; LC-MS/MS; esi; matrix effect; phospholipids; tissue distribution studies