| Author: | Lin, Xuewei |
| Title: | Rapid authentication of red wine and chiral recognition of drugs by mass spectrometry |
| Advisors: | Yao, Zhong-ping (ABCT) |
| Degree: | Ph.D. |
| Year: | 2024 |
| Department: | Department of Applied Biology and Chemical Technology |
| Pages: | xxvii, 187 pages : color illustrations |
| Language: | English |
| Abstract: | Mass spectrometry (MS) is a powerful and versatile analytical tool with advantages such as high sensitivity and high speed. The process of mass spectrometry involves the ionization of chemical compounds to produce charged molecules or fragments, followed by measuring their mass-to-charge ratios. There are various types of mass spectrometers, with different advantages and applications, including time-of-fligh, quadrupole, ion trap, orbitrap and Fourier transform ion cyclotron resonance mass spectrometers. MS has numerous applications in various fields such as chemistry, pharmacology, forensic science, environmental science and biology. In this thesis, two studies involving MS-based analytical methods are performed, including authentication of red wine and chiral recognition of drugs. The importance of authentication of red wine as well as current analytical methods for the authentication have been introduced in Chapter 1. Red wine, among the most consumed alcoholic drinks, occupies a great market worldwide. Due to its commercial value, though considerable efforts have been made to protect both consumers and producers, counterfeiting of wine has long time been a severe problem concerning dilution, prohibited addition and mislabeling of brands or years. The authenticity of wine with regard to its origins, vintage years, grape varieties, etc., has thus become an important issue. Developing a rapid, simple and accurate method to authenticate plenty of samples with complex features is required. Two direct mass spectrometry techniques, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and direct analysis in real time mass spectrometry (DART-MS), were employed to analyze red wine in this project. The two methods were found to be complementary to each other in terms of mass ranges and detected compounds. A simple, rapid and high-throughput approach was developed for authentication of red wine for the first time, by combining spectral results from MALDI-MS and DART-MS. By coupling with orthogonal partial least squares discrimination analysis (OPLS-DA), this approach allowed the successful classification of 535 wine samples collected from 8 key wine-producing countries, with the correct classification rates of 100% on the calibration set and over 90% on the validation set for almost all countries, and 26 potential characteristic markers were selected. Compared to one single technique, this approach allowed the detection of more compound ions, and with higher fitting and predictive consequences. The satisfactory differentiation results of vintages and grape varieties further verified the robustness of the approach. This study demonstrated the feasibility of combining multiple mass spectrometric techniques for wine analysis, which can be extended to other fields or combinations of other analytical techniques. In Chapter 2, MS was applied for chiral recognition of chiral drugs. Chirality plays an important role in various fields, including chemistry, biology, pharmaceutical science, etc. Chiral compounds such as amino acids, proteins, enzymes, and nucleosides are vital for life. The biological activities of the drug enantiomers can vary significantly due to their structural differences, emphasizing the important role of chiral recognition of drugs. Chiral recognition by MS is typically achieved by analysis of complexes found between enantiomers and chiral selectors, and tandem mass spectrometry (MS/MS) is commonly used for such analyses due to its simplicity and high reproducibility. In this thesis, MS/MS was utilized for the discrimination of several types of chiral drugs. Four chiral drugs, ofloxacin, clopidogrel, omeprazole and bupivacaine, were investigated first, by introducing various chiral selectors, such as amino acids and cyclodextrins. The influence of metal ions was investigated and optimized as well. For the first three drugs, various complex ions we reformed by introducing chiral selectors. The results showed that using MS/MS, chiral differentiation could be obtained with all drugs studied. The MS/MS analysis of singly charged trimers [ofloxacin+2Pro+Cu−H]+ with proline (Pro) as the chiral selector allowed effective analysis with a chiral recognition ratio (CR) of 1.44±0.13, as well as enantiomeric excess determination of ofloxacin, the calibration curve of which gave a linear coefficient of 0.9878. The copper-bound trimers [clopidogrel+2Trp+Cu−H]+ with tryptophan (Trp) as the chiral selector exhibited the highest level of chiral discrimination for clopidogrel, with a CR value of 2.16±0.04. The doubly charged complex ions [omeprazole+2Trp+K+H]2+ contributed to a significant CR value of 0.27±0.15 for the effective discrimination of omeprazole enantiomers. Interestingly, for bupivacaine, the MS/MS of its self-assembly trimers [3bupivacaine+H]+ allowed differentiation of the enantiomers without any chiral selectors. However, the chiral analysis results obtained by the four chiral drugs were different, mainly due to the different sizes and chemical structures of the drugs, which had a significant impact on the formation of cluster ions and the binding strength within ions. Overall, these findings highlighted the varying chiral effects of drugs with different spatial structures, which might give instructions for the selection of selectors for chiral compounds. In Chapter 3, a further study was performed with omeprazole as a representative chiral drug first due to its excellent discrimination results, and the use of different types of chiral selectors was studied, including one amino acid, combinations of two amino acids, and dipeptides, with or without copper-bound, and the differences of complex ions were compared and discussed. Interestingly, it was found that the chiral discrimination of omeprazole could be achieved by introducing these three types of chiral selectors with dipeptides as the best, followed by two amino acids, and one amino acid the last. Results showed that increased numbers of complex ions were observed with dipeptides as the chiral selectors, indicating stronger binding between omeprazole and dipeptides. Chiral discrimination was observed with all dipeptides chiral selectors tested, even with only one chiral center in dipeptides or different orders of amino-acid residues in dipeptides. The application of peptides as chiral selectors was also extended to the analysis of other chiral drugs, e.g., clopidogrel. The results indicated the exceptional efficacy of peptides as the chiral selectors for the chiral MS analysis and their potential for other chiral analyses, e.g., the design of chiral columns for chiral analysis by high-performance liquid chromatography. In Chapter 4, the results and general conclusions of the two studies were summarized, together with the prospects for them, especially for the second study, further investigations are needed. |
| Rights: | All rights reserved |
| Access: | open access |
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