In-tip Solid Phase Microextraction for High Throughput Drug Analysis

In-tip Solid Phase Microextraction for High Throughput Drug Analysis PDF Author: Wei Xie
Publisher:
ISBN:
Category :
Languages : en
Pages : 312

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Book Description
This thesis describes the design of a convenient format of solid phase microextraction (SPME) for bioanalysis in pharmaceutical industry and the validation of the approach to the application. An automated in-tip SPME technique coupled with liquid chromatography (LC) and tandem mass spectrometry (MS/MS) for high throughout drug analysis has been developed and applied to the quantitative determination of various drug compounds in different biological fluids from drug discovery to clinical development. The initial research in this thesis focused on a proof-of-concept study using manual multi-fiber approach to determine a drug compound in human plasma from a clinical trial. The proof-of-concept was achieved based on the validation data and a head-to-head comparison with conventional liquid-liquid extraction (LLE) method. An in-tip SPME technique was then proposed to explore the feasibility of SPME automation and two approaches of preparing in-tip SPME fibers were developed including fiber-packed and sorbent-packed fiber preparation. A simple and high throughput in-tip SPME fiber fabricating procedure based on polymer monoliths using photo-polymerization was introduced to prepare 96 fibers simultaneously. The biggest advantage of the in-tip SPME technique is that it is simple and easy to use for automation without introducing any additional devices and in the meantime, the simplicity of SPME is maintained. Automated in-tip SPME was applied to routine drug analysis in drug discovery and development environment. One case study involved the determination of vitamin D3 in human serum with derivatization and the in-tip SPME approach was compared with traditional LLE method using either tubes or 96-well plate extraction. Another study was to use hydrophilic interaction chromatography (HILIC) -MS/MS to determine three polar compounds, imipenem (IMP), cliastatin (CIL) and [beta]-lactamase inhibitor (BLI) simultaneously in different biological fluids including rat plasma and mouse blood. The results from both studies clearly demonstrated that in-tip SPME could be used as an alternative sample preparation method in bioanalytical analysis. Matrix effects in bioanalysis using automated in-tip SPME and LC-MS/MS were then thoroughly evaluated for the first time. Our study indicated that the assumption that SPME should provide sample clean up as effective as or better than solid phase extraction (SPE) with no or minimal matrix effects might not be always true, and matrix effects should be investigated in any SPME assays in bioanalysis.

In-tip Solid Phase Microextraction for High Throughput Drug Analysis

In-tip Solid Phase Microextraction for High Throughput Drug Analysis PDF Author: Wei Xie
Publisher:
ISBN:
Category :
Languages : en
Pages : 312

Get Book Here

Book Description
This thesis describes the design of a convenient format of solid phase microextraction (SPME) for bioanalysis in pharmaceutical industry and the validation of the approach to the application. An automated in-tip SPME technique coupled with liquid chromatography (LC) and tandem mass spectrometry (MS/MS) for high throughout drug analysis has been developed and applied to the quantitative determination of various drug compounds in different biological fluids from drug discovery to clinical development. The initial research in this thesis focused on a proof-of-concept study using manual multi-fiber approach to determine a drug compound in human plasma from a clinical trial. The proof-of-concept was achieved based on the validation data and a head-to-head comparison with conventional liquid-liquid extraction (LLE) method. An in-tip SPME technique was then proposed to explore the feasibility of SPME automation and two approaches of preparing in-tip SPME fibers were developed including fiber-packed and sorbent-packed fiber preparation. A simple and high throughput in-tip SPME fiber fabricating procedure based on polymer monoliths using photo-polymerization was introduced to prepare 96 fibers simultaneously. The biggest advantage of the in-tip SPME technique is that it is simple and easy to use for automation without introducing any additional devices and in the meantime, the simplicity of SPME is maintained. Automated in-tip SPME was applied to routine drug analysis in drug discovery and development environment. One case study involved the determination of vitamin D3 in human serum with derivatization and the in-tip SPME approach was compared with traditional LLE method using either tubes or 96-well plate extraction. Another study was to use hydrophilic interaction chromatography (HILIC) -MS/MS to determine three polar compounds, imipenem (IMP), cliastatin (CIL) and [beta]-lactamase inhibitor (BLI) simultaneously in different biological fluids including rat plasma and mouse blood. The results from both studies clearly demonstrated that in-tip SPME could be used as an alternative sample preparation method in bioanalytical analysis. Matrix effects in bioanalysis using automated in-tip SPME and LC-MS/MS were then thoroughly evaluated for the first time. Our study indicated that the assumption that SPME should provide sample clean up as effective as or better than solid phase extraction (SPE) with no or minimal matrix effects might not be always true, and matrix effects should be investigated in any SPME assays in bioanalysis.

Handbook of Solid Phase Microextraction

Handbook of Solid Phase Microextraction PDF Author: Janusz Pawliszyn
Publisher: Elsevier
ISBN: 0123914493
Category : Science
Languages : en
Pages : 497

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Book Description
The relatively new technique of solid phase microextraction (SPME) is an important tool to prepare samples both in the lab and on-site. SPME is a "green" technology because it eliminates organic solvents from analytical laboratory and can be used in environmental, food and fragrance, and forensic and drug analysis. This handbook offers a thorough background of the theory and practical implementation of SPME. SPME protocols are presented outlining each stage of the method and providing useful tips and potential pitfalls. In addition, devices and fiber coatings, automated SPME systems, SPME method development, and In Vivo applications are discussed. This handbook is essential for its discussion of the latest SPME developments as well as its in depth information on the history, theory, and practical application of the method. - Practical application of Solid Phase Microextraction methods including detailed steps - Provides history of extraction methods to better understand the process - Suitable for all levels, from beginning student to experienced practitioner

Handbook of Solid Phase Microextraction

Handbook of Solid Phase Microextraction PDF Author: Janusz Pawliszyn
Publisher: Elsevier
ISBN: 0124160174
Category : Science
Languages : en
Pages : 497

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Book Description
The relatively new technique of solid phase microextraction (SPME) is an important tool to prepare samples both in the lab and on-site. SPME is a "green" technology because it eliminates organic solvents from analytical laboratory and can be used in environmental, food and fragrance, and forensic and drug analysis. This handbook offers a thorough background of the theory and practical implementation of SPME. SPME protocols are presented outlining each stage of the method and providing useful tips and potential pitfalls. In addition, devices and fiber coatings, automated SPME systems, SPME method development, and In Vivo applications are discussed. This handbook is essential for its discussion of the latest SPME developments as well as its in depth information on the history, theory, and practical application of the method. Practical application of Solid Phase Microextraction methods including detailed steps Provides history of extraction methods to better understand the process Suitable for all levels, from beginning student to experienced practitioner.

Solid Phase Microextraction

Solid Phase Microextraction PDF Author: Sue Ann Wercinski
Publisher: CRC Press
ISBN: 9781439832387
Category : Science
Languages : en
Pages : 274

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Book Description
An explanation of proven methods of chemical analysis, focusing on the myriad applications of solid phase microextraction (SPME) to laboratories performing high-sample throughput, quick sample turnaround time, low detection levels, and dirty sample matrices. It supplies commentary on developments in SPME technology from its inventor, Janusz Pawliszyn.

Evolution of Solid Phase Microextraction Technology

Evolution of Solid Phase Microextraction Technology PDF Author: Janusz Pawliszyn
Publisher: Royal Society of Chemistry
ISBN: 1839166800
Category : Science
Languages : en
Pages : 663

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Book Description
Solid Phase Microextraction (SPME) is a flexible and convenient sampling and sample preparation technique that extracts different kinds of analytes, including both volatile and non-volatile, without the use of a solvent. The technique facilitates fast, simple and automated determination of target analytes in a range of matrices. As it offers a green methodology, it is growing in popularity as an alternative tool in analytical chemistry to traditional methods. This book follows on in spirit from the editors' previous title, Applications of Solid Phase Microextraction and will introduce the reader to breakthrough methodologies and cutting edge applications. Although it assumes a good degree of SPME knowledge, an overview of the fundamentals is given before taking the reader through an update of the field. The reader will learn the basic principles and advantages of different SPME formats including the stir bar extraction techniques, thin film SPME, Bio-SPME, and new trends in different coatings. Applications in complex media, including food analysis, drug residues and bioanalysis are covered. Bringing together leading sample preparation academics from around the world, the editor has put together an informative new book, suitable for analytical chemists and practitioners utilising SPME tools in their research.

Sample Preparation in LC-MS Bioanalysis

Sample Preparation in LC-MS Bioanalysis PDF Author: Wenkui Li
Publisher: John Wiley & Sons
ISBN: 111927429X
Category : Science
Languages : en
Pages : 384

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Book Description
Revised and Expanded Handbook Provides Comprehensive Introduction and Complete Instruction for Sample Preparation in Vital Category of Bioanalysis Following in the footsteps of the previously published Handbook of LC-MS Bioanalysis, this book is a thorough and timely guide to all important sample preparation techniques used for quantitative Liquid Chromatography–Mass Spectrometry (LC-MS) bioanalysis of small and large molecules. LC-MS bioanalysis is a key element of pharmaceutical research and development, post-approval therapeutic drug monitoring, and many other studies used in human healthcare. While advances are continually being made in key aspects of LC-MS bioanalysis such as sensitivity and throughput, the value of research/study mentioned above is still heavily dependent on the availability of high-quality data, for which sample preparation plays the critical role. Thus, this text provides researchers in industry, academia, and regulatory agencies with detailed sample preparation techniques and step-by-step protocols on proper extraction of various analyte(s) of interest from biological samples for LC-MS quantification, in accordance with current health authority regulations and industry best practices. The three sections of the book with a total of 26 chapters cover topics that include: Current basic sample preparation techniques (e.g., protein precipitation, liquid-liquid extraction, solid-phase extraction, salting-out assisted liquid-liquid extraction, ultracentrifugation and ultrafiltration, microsampling, sample extraction via electromembranes) Sample preparation techniques for uncommon biological matrices (e.g., tissues, hair, skin, nails, bones, mononuclear cells, cerebrospinal fluid, aqueous humor) Crucial aspects of LC-MS bioanalytical method development (e.g., pre-analytical considerations, derivation strategies, stability, non-specific binding) in addition to sample preparation techniques for challenging molecules (e.g., lipids, peptides, proteins, oligonucleotides, antibody-drug conjugates) Sample Preparation in LC-MS Bioanalysis will prove a practical and highly valuable addition to the reference shelves of scientists and related professionals in a variety of fields, including pharmaceutical and biomedical research, mass spectrometry, and analytical chemistry, as well as practitioners in clinical pharmacology, toxicology, and therapeutic drug monitoring.

Analytical Microextraction Techniques

Analytical Microextraction Techniques PDF Author: M. Valcárcel
Publisher: Bentham Science Publishers
ISBN: 1681083795
Category : Science
Languages : en
Pages : 430

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Book Description
Sample treatment has been the focus of intensive research in the last 20 years since it still remains a bottleneck in precise analytical procedures. The low concentration of the target analytes, the large amount of potential interfering agents and the incompatibility of the sample matrix with the instrumental techniques are the main reasons for these bottlenecks. In most of these methods, sample treatment is an unavoidable step and it has a clear influence on the quality (sensitivity, selectivity, and accuracy) of the final analytical results. While the usefulness of microextraction techniques has been established, their complete acceptance in analytical laboratories (including official methods of analysis) depends on their successful automation and integration with conventional analytical instrumentation. Analytical Microextraction Techniques presents comprehensive information about several analytical methods that are useful in the laboratory. These include: sorptive microextraction, solid and liquid phase microextraction, packed sorbent microextraction, miniaturized dispersive solid-phase extraction, thin film and nanoparticle based techniques, and membrane-based techniques. This is a vital reference on microextraction and sample preparation techniques for applied chemistry students, analytical chemists and laboratory technicians.

Solid Phase Microextraction

Solid Phase Microextraction PDF Author: Gangfeng Ouyang
Publisher: Springer
ISBN: 366253598X
Category : Science
Languages : en
Pages : 313

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Book Description
This book offers comprehensive information on the developments and applications of the solid phase microextraction (SPME) technique. The first part of the book briefly introduces readers to the fundamentals of SPME, while subsequent sections describe the applications of SPME technique in detail, including environmental analysis (air, water, soil/sediments), food analysis (volatile/nonvolatile compounds), and bioanalysis (plants, animal tissues, body fluids). The advantages and future challenges of the SPME technique are also discussed. Including recent research advances and further developments of SPME, the book offers a practical reference guide and a valuable resource for researchers and users of SPME techniques. The target audience includes analytical chemists, environmental scientists, biological scientists, material scientists, and analysts, as well as students at universities/institutes in related fields. Dr. Gangfeng Ouyang is a Professor at the School of Chemistry and Chemical Engineering, Sun Yat-sen University, China. Dr. Ruifen Jiang is an Associate Professor at the School of Environment, Jinan University, China.

Applications of Solid Phase Microextraction

Applications of Solid Phase Microextraction PDF Author: Janusz Pawliszyn
Publisher: Royal Society of Chemistry
ISBN: 9780854045259
Category : Science
Languages : en
Pages : 680

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Book Description
Solid Phase Microextraction (SPME) has been introduced as a modern alternative to current sample preparation technology, and has a wide range of applications. Focusing on quantitative aspects of analysis, Applications of Solid Phase Microextraction aims to describe these applications. In industry, practical uses of SPME can be found in environmental, food, pharmaceutical, clinical and forensic applications, all of which are described in this book. Important scientific applications such as reaction monitoring, characterization of coatings and distributions of analytes in natural multiphase systems are also discussed. Throughout there are descriptions of new technologies, including new coatings and interfaces for analytical instrumentation (SPME/LC and SPME/CE), automation and calibration processes. Written by internationally recognised experts, edited by the scientist involved in the research since its infancy, and encompassing a wide range of applications, this book will be ideal for anyone wishing to explore the feasibility of using SPME technology.

Developments and Applications of Solid Phase Microextraction (SPME) Coupled to Direct Analysis in Real Time (DART) and Approaches Towards Small Volume Analysis

Developments and Applications of Solid Phase Microextraction (SPME) Coupled to Direct Analysis in Real Time (DART) and Approaches Towards Small Volume Analysis PDF Author: Tijana Vasiljevic
Publisher:
ISBN:
Category : Sample preparation (Chemistry)
Languages : en
Pages : 300

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Book Description
Solid phase microextraction (SPME) has been rapidly developing since its invention in 1990. Due to a flexible design and the ability to implement various extractive coatings, SPME has found use in numerous applications. One such application is the coupling of SPME to Direct Analysis in Real Time (DART), an ambient ionization mass spectrometry (AIMS) technique. AIMS techniques completely eliminate the use of chromatography, reducing lengthy workflows and improving time-efficiency. SPME coupled to DART-MS has been quite successful in achieving low detection limits and reproducible results in bioanalytical applications. These successes are mostly due to the excellent preconcentrating and interference resisting abilities of SPME coatings and detection capabilities of DART-MS. Certainly, as a novel technique, many aspects of SPME-DART-MS are yet to be explored. Hence, this thesis investigated fundamental aspects of SPME-DART-MS, in addition to exploring novel applications, such as detection of prohibited substances in small bio-volumes (i.e., ≤ 25 μL of oral fluid (OF) and human blood) and implementation of SPME-DART-MS as high-throughput technology for quantitation of opioids in urine and human plasma in less than 1.5 h for a set of 96 samples. Coupling of SPME to portable DART-MS instrumentation was investigated for on-site, in vivo drug detection in samples of OF as a potential tool of law enforcement, reporting detection limits that are below those proposed by regulatory agencies. Additionally, the use of biocompatible plastic materials such as polyetheretherketone (PEEK) was investigated as a potential alternative material for the manufacturing of SPME devices for DART-MS, which are usually made of stainless steel (SS). Performance of the PEEK devices was similar to those of SS, allowing for their use in quantification of drugs-of-abuse (DoAs) in OF and urine at low parts-per-billion levels (ppb). In addition, OF samples following coffee consumption from a female volunteer were used to monitor caffeine half-life. The results were in compliance with established half-life of caffeine reported in literature, and highlighted the potential of the PEEK devices for in vivo buccal swabbing testing. Another novel application of SPME described in this thesis was the development of miniaturized SPME devices "minitips" for analysis of small volumes. The analysis of small sample volumes (biofluids, tissues, and cells) has become more common within the scientific community in the last few years. For this type of analysis, very sensitive instrumental platforms and sample preparation methods are required to obtain qualitative and quantitative information. Hence, the SPME minitip format was introduced, and the tip apex was coated with 1 millimeter (mm) of polyacrylonitrile (PAN) and in-house-synthesized N-vinylpyrrolidone-co-divinylbenzene, also known as hydrophilic lipophilic balance (HLB) particles. Robustness, extraction efficiency, repeatability, reusability, and matrix effect (ME) assessment yielded good results. Benzodiazepines were extracted from 15 μL of phosphate buffer saline (PBS) and urine, and certain DoAs were extracted from 1 μL of OF using LC-MS/MS. Very good figures of merit were obtained, with limits of detection (LODs) and quantitation (LOQs) in the lower ppb range. DoAs were also extracted from 1 μL of blood by directly coupling the SPME minitips to nanoelectrospray ionization (nESI) devices. The SPME HLB minitips were also used for untargeted metabolomic profiling of caviar eggs via liquid chromatography high resolution mass spectrometry (LC/HRMS), thereby showing that despite introduced dilution, satisfactory results can be obtained. Indeed, good statistical separation of caviar eggs was observed, in addition to extracting well over a hundred significant features. Lastly, this thesis also details application of SPME for untargeted metabolomics profiling of patient affected with a genetic condition known as malignant hyperthermia (MH). Small human muscles obtained from Toronto General Hospital were sampled using SPME fibers and analysed via LC/HRMS using an untargeted metabolomics approach. Potential disease related compounds (i.e., biomarkers) were found, aiding in the elucidation of the biochemical pathways affected in patients with MH. The accepted diagnostic tool of MH is a highly invasive procedure which involves excision of a portion of the Gracilis muscle. Hence the prospect of using SPME as minimally invasive diagnostic tool was discussed. As this thesis shows, the opportunities of SPME are many; and its continuous development will most likely require efforts and collaboration from experts in numerous fields.