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Aspects of matrix and analyte effects in clinical pharmacokinetic sample analyses using LC-ESI/MS/MS - Two case examples
Journal article   Open access   Peer reviewed

Aspects of matrix and analyte effects in clinical pharmacokinetic sample analyses using LC-ESI/MS/MS - Two case examples

Guohua An, Thanh Bach, Inas Abdallah and Demet Nalbant
Journal of pharmaceutical and biomedical analysis, Vol.183, 113135
05/10/2020
DOI: 10.1016/j.jpba.2020.113135
PMCID: PMC7216566
PMID: 32062015
url
https://www.ncbi.nlm.nih.gov/pmc/articles/7216566View
Open Access

Abstract

The increasing focus on high throughput sample analysis has led to the common practice of using simplest sample preparation method possible (i.e. protein precipitation) and shortest sample run-time possible. This means that there will be two aspects of compromise: the first compromise is made between sample cleanliness and sample preparation speed since protein precipitation does not provide very clean final extract; the second compromise is made between peak separation and run-time, meaning that sometimes overlap or co-elution of some peaks has to be accepted. The first compromise may lead to matrix effect, which is caused by co -eluting endogenous substances such as phospholipids. The second compromise can result in analyte effect, which is caused by co-eluting analyte( s). We have encountered the issue of matrix/analyte-mediated ion suppression in multiple preclinical and clinical pharmacokinetic projects during bioanalytical method development/validation or biological sample analysis of many small molecule drugs. As these matrix/analyte effects could occur in different situations with different "syndromes", sometimes it can be easily overlooked, leading to unreliable result, poor sensitivity, and prolonged assay development process. To increase the awareness of this important issue, in this paper we presented two real case examples on signal suppression caused by either endogenous phospholipids or co -eluting analyte. (C) 2020 Elsevier B.V. All rights reserved.
Physical Sciences Chemistry Chemistry, Analytical Life Sciences & Biomedicine Pharmacology & Pharmacy Science & Technology

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