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Automated High-throughput Analysis of Multi-class Multi-residue Pharmaceutical Drugs in Animal Tissue Using Solid Phase Microextraction

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Date

2020-05-06

Authors

Khaled, Abir

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Publisher

University of Waterloo

Abstract

The use of veterinary pharmaceuticals in today´s intensive farming of food-producing animals is essential for the humane treatment of animals and as well as for the prevention of outbreaks of infectious diseases. Improper administration of these drugs may lead to excessive levels of drug residues in the edible tissues of treated animals, posing a potentially serious risk to human health. Accordingly, monitoring of veterinary drug residues is an integral component of food safety programs worldwide. Reliable analytical methods play a crucial role in the endeavor to enforce regulations surrounding the use of veterinary drugs in food-producing animals. Recent advancements in liquid chromatography (LC) and mass spectrometry (MS) have facilitated the development of multi-class, multi-residue analytical methods capable of screening a large number of analytes in a single analytical run. However, due to the complexity of biological tissues, the large number of veterinary drugs to be monitored, and the wide variation in their physico-chemical properties, sample preparation constitute a major bottleneck of their analytical workflow. Sample preparation is critical in relation to sample turnaround and the reliability of the analytical outcome. In this context, an ideal sample preparation method for multi-class multi-residue analysis should offer enough non-selectivity so as to cover a wide range of polarities and thus allow extraction of as many analytes as possible, while at the same time delivering a high degree of sample clean-up so as to reduce matrix effects. Solid phase microextraction (SPME) has been demonstrated as a suitable sample preparation tool that allows isolation/enrichment of multiple analytes in addition to excellent sample clean-up. The main objective of this thesis was to develop automated high-throughput analytical methods for quantitative analysis of multi-class multi-residue veterinary drugs in meat using liquid chromatography and mass spectrometric techniques. The introductory chapter offers an extensive review of veterinary drug classes used in food animal production and the current analytical methodologies used for their analysis. In addition, chapter 1 offers an extensive review of the most commonly used generic sample preparation techniques. The experimental section of this thesis is constituted of four chapters, 2-5. Chapter 2 describes the development and validation of an automated high-throughput direct-immersion SPME method for the quantitative analysis of 77 veterinary drugs belonging to more than 12 classes of drug compounds in homogenized tissue from chicken. In chapter 3, the scope of the SPME method presented in chapter 2 was expanded to a new matrix (beef tissue), and for detection of an additional 25 analytes. Moreover, the work also encompassed a comparison of the SPME method to two well-documented sample preparation procedures, namely solvent extraction (SE) and the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method. Chapter 4 and 5 present works aimed to increase efficiency and sample throughput through the development of rapid screening methods that involve the direct coupling of SPME to mass spectrometry. For this purpose, two different ambient ionization mass spectrometry techniques were studied, namely coated blade spray (CBS) and direct analysis in real time (DART). Finally, chapter 6 summarizes the main findings of this work and provides future directions to be considered with regards to the applicability of SPME towards multi-residue analysis of animal tissue.

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Keywords

solid phase microextraction, veterinary drugs, multi-class multi-residue analysis, high-throughput analysis, ambient ionization mass spectrometry, liquid chromatography, mass spectrometry, direct analysis in real time, coated blade spray

LC Keywords

Veterinary drugs, Veterinary drugs--Analysis, Solid-phase analysis, High throughput screening (Drug development), Mass spectrometry, Liquid chromatography

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