Effects of Sample Processing Techniques and Instrument Model on Matrix Effect in LC-MS/MS for a Model Drug

Abstract

The common perception that utilization of liquid chromatography-mass spectrometer (LC-MS) guarantees selectivity has now been challenged by a number of reported examples for the lack of selectivity due to ion suppression or enhancement caused by the sample matrix and interference from metabolites. It has been observed that an efficient sample preparation technique can reduce the matrix effect significantly. This research aims to evaluate the synergistic effect of sample processing technique and instrument model on matrix effect in LC-MS analysis by post-extraction addition and post-column infusion methods. Accordingly, different sample processing techniques, i.e., protein precipitation, liquid–liquid extraction, and solid phase extraction were evaluated for model drug, Esomeprazole, and samples processed with all the three techniques analyzed on three different MS models of AB Sciex, i.e., API-3000, API-3200, and API-4000. Samples were analyzed using Discovery C18 column and mobile phase acetonitrile: 10 mM ammonium acetate buffer (pH 4.8–5.2) :: 80:20, v/v. Results visibly showed that matrix effect was nullified by analyzing samples of liquid–liquid extraction technique on API-3200 and indicated that instrument model and sample processing technique have synergistic effect in contribution to matrix effect. Therefore, one should evaluate matrix effect in the early stage of method development and combine effective sample-processing technique with appropriate instrument model.

Keywords:

• instrument model
• LC-MS
• matrix effect
• process efficiency
• sample processing technique
• structural analog internal standard

Acknowledgments

This paper is part of PhD thesis of Poonam Vats and the first author would like to thank Ranbaxy Research Laboratories, Gurgaon, India, for carrying out this work.