Gas Chromatography for the Analysis of Drugs Michelle L
Total Page：16
File Type：pdf, Size：1020Kb
Seton Hall University eRepository @ Seton Hall Seton Hall University Dissertations and Theses Seton Hall University Dissertations and Theses (ETDs) Spring 5-16-2015 QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) Extraction – Gas Chromatography for the Analysis of Drugs Michelle L. Schmidt [email protected] Follow this and additional works at: https://scholarship.shu.edu/dissertations Part of the Analytical Chemistry Commons, and the Medicinal-Pharmaceutical Chemistry Commons Recommended Citation Schmidt, Michelle L., "QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) Extraction – Gas Chromatography for the Analysis of Drugs" (2015). Seton Hall University Dissertations and Theses (ETDs). 2060. https://scholarship.shu.edu/dissertations/2060 QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) Extraction – Gas Chromatography for the Analysis of Drugs BY Michelle L. Schmidt DISSERTATION Submitted to the Department of Chemistry and Biochemistry at Seton Hall University in partial fulfillment of the requirements for the degree of Doctor of Philosophy. May, 2015 1 © Michelle L. Schmidt 2015 2 We certify that we have read this dissertation and that in our opinion it is adequate to scientific scope and quality as a dissertation for the degree of Doctor of Philosophy. APPROVED _________________________________________________________ Nicholas H. Snow, Ph.D Research Mentor and Chair, Department of Chemistry and Biochemistry _________________________________________________________ Yuri V. Kazakevich, Ph.D Member of the Dissertation Committee _________________________________________________________ Sergiu M. Gorun, Ph.D Member of the Dissertation Committee 3 ACKNOWLEDGEMENTS I would like to thank Dr. Nicholas H. Snow for his continued guidance, input, and advice throughout my time at Seton Hall University and whose help was invaluable and deeply appreciated. He allowed me to become an independent, ‘think outside the box’ scientist and I cannot thank him enough. I would also like to thank Dr. Yuri Kazakevich and Dr. Sergiu Gorun for their input on both my dissertation and aid during my research. In addition to Drs. Snow, Kazakevich and Gorun, I would also like to thank Dr. Stephen Kelty and Dr. Cecelia Marzabadi, all of whom served on my matriculation committee and have provided research suggestions. I would like to thank Shimadzu, for their lending of the GC-MS/MS used in this research, and LECO, for their aid in use of the GCxGC-TOFMS. Both provided technical support, which was much appreciated. I would also like to thank Sanofi-Aventis and the Dr. Robert DeSimone Dissertation Fellowship in providing financial support for this research as well as the Philanthropic Educational Organization for the awarding of a $15,000 scholarship that was used toward my research. I would like to extend a special thanks to the Separation Science Group at Seton Hall University. Firstly, to those that I worked closest with in the lab throughout my time as a Ph.D. student, Dr. Brian Barnes, Dr. Shilpi Chopra, Dr. Ramkumar Dhandipani, Anumeha Muthal, Tom DelMastro, and Leanne Mocniak. The ability to work side by side and learn from each other was invaluable and I formed lasting friendships that I am extremely grateful to have. Lastly, I want to thank Julianne Berger and Nicole Curto, 4 who I met during my first year at Seton Hall. In them I truly found life long friends. We helped each other throughout our journey at Seton Hall and I don’t know how I would have gotten through it all without them. Most importantly, I would like to extend my greatest thanks and appreciation to my family and friends, particularly my mom, Joan; dad, Mike; sister, Andrea; fiancé, Rob; and past mentor, Dr. Lawrence Quarino, all of whom without this would not have been possible. They pushed me to be my best self and pursue my love of chemistry to obtain my Ph.D. They are the anchor that keeps my feet on the ground. It is because of them that I have the drive and passion to never give up on my dreams and always strive to accomplish my goals. Thank you mom and dad for shaping me into the person I am and for teaching me that if I work hard and put my mind to it, I can achieve anything. You gave me wings so I could fly. Finally, though they are no longer with me, my grandma and pop-pop always supported me in my dreams and endeavors and I hope I have made them proud. They are the wings that keep my heart in the clouds. 5 LIST OF FIGURES Figure 1-1. Structure of endcapped primary secondary amine (PSA) solid phase extraction (SPE) packing .................................................................................................. 26 Figure 1-2. Methodology of the LLE and clean up step for the original, AOAC 2007.01, and EN 15662 QuEChERS methods. Adapted from The UCT Pesticide Residue Analysis QuEChERS Information Booklet [8] ................................................................. 27 Figure 1-3. The three terms in the Van Deemter equation. A: eddy diffusion; B: longitudinal diffusion; C: mass transfer. Adapted from Y. Kazakevich Separations Introduction Lecture Slides [59] ...................................................................................... 52 Figure 1-4. The three terms in a Van Deemter plot (left) and the various gases as how they appear in the Van Deemter plot (right) ..................................................................... 53 Figure 1-5. Split (left) and splitless (right) injection. Adapted from Y. Kazakevich GC Injectors Lecture Slides [60]. ............................................................................................ 56 Figure 1-6. Schematic of an electron ionization (EI) source ............................................ 59 Figure 1-7. Schematic of a quadrupole mass analyzer. Adapted from P. Gates Gas Chromatography Mass Spectrometry (GC/MS): Figure 2 [61] ........................................ 60 Figure 1-8. Schematic of a continuous dynode electron multiplier. Adapted from J. Benedikt, A. Hecimovic, D. Ellerweg, and A. von Keudell. J Phys D-Appl Phys. 45(50) (2012) [62]. ....................................................................................................................... 61 Figure 2-1A. Overlaid chromatograms of a DCM-tea sample shake, LLE with ACN and salts, d-SPE with ACN and tea sample only, and the complete QuEChERS method ...... 74 Figure 2-1B. Top: Chromatogram depicting the peak area of caffeine at 5.704min without QuEChERS. Bottom: Chromatogram depicting the increased peak area of caffeine at 5.716min with QuEChERS as well as decreased matrix interference peaks .................... 75 Figure 2-2. Optimization of the pH during the initial sonication of lose tea in deionized water. ................................................................................................................................. 77 6 Figure 2-3. The effect of time on the initial sonication time of loose tea in deionized water (left) and the resulting plot of peak area vs. time as a kinetic study. ...................... 78 Figure 2-4. The effect of temperature during the initial sonication of loose tea in deionized water as a thermodynamic study. .................................................................... 79 Figure 2-5. The effect of the salt ratio on the amount of organic solvent separated from the aqueous phase and the extraction of matrix interferences .......................................... 81 Figure 2-6. Optimization of salt ratio amount during the LLE step of the QuEChERS method ............................................................................................................................... 82 Figure 2-7. Optimization of the salt type during the LLE step of the QuEChERS method. ........................................................................................................................................... 83 Figure 2-8. Optimization of the ratio of organic solvent to aqueous tea sample during the LLE step of the QuEChERS method. ............................................................................... 86 Figure 2-9. Optimization of the organic solvent type during the LLE step of the QuEChERS method. ......................................................................................................... 87 Figure 2-10. The effect of time on the sonication time during the LLE step in the QuEChERS method (left) and the resulting plot of peak area vs. time as a kinetic study. ........................................................................................................................................... 89 Figure 2-11. The effect of time on the sonication time during the d-SPE step in the QuEChERS method (left) and the resulting plot of peak area vs. time as a kinetic study. ........................................................................................................................................... 90 Figure 2-12. The effect of temperature during the LLE step in the QuEChERS method. 92 Figure 2-13. The effect of temperature during the d-SPE step in the QuEChERS method. ........................................................................................................................................... 93 Figure 2-14. Calibration curve from the method validation of the optimized QuEChERS extraction. .......................................................................................................................... 95 Figure 2-15. Linearity of caffeine from the method validation of the