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Biológiailag aktív vegyületek vizsgálata elválasztástechnikai módszerekkel kapcsolt tömegspektrometriás technikákkal
Virág Dávid
Pharmacology and Pharmacy
Dr. Szőke Éva
SE Egyetemi Gyógyszertár Gyógyszerügyi Szervezési Intézet
2022-05-05 00:00:00
A gyógyszerészeti tudományok korszerű kutatási irányai
Dr. Antal István
Dr. Ludányi Krisztina
Dr. Kéki Sándor
Dr. Őrfi László
Dr. Szökő Éva
Dr. Deme Ruth
Dr. Takátsy Anikó
In the first part of my doctoral research, I developed an LC-MS/MS based bioanalytical method for the simultaneous determination of serotonin and kynurenin with amino acids (valine, leucine, isoleucine, tyrosine and tryoptophan) in human plasma. The procedure was able to separate isomeric amino acids (leucine, isoleucine) as well as to determine the analytes quantitatively, despite the significant differences in their concentrations. The simple sample preparation procedure, the proper selection of the calibration method, and the high resolution chromatographic method in combination with the MS/MS measurements enabled the analysis of a large number of samples. Validation of the analytical method was carried out based on the so-called ”fit-for-purpose” approach combining authentic analyte in surrogate matrix and standard addition method resulting in a successful validation of the method. The concentration data obtained from this study supported a comprehensive clinical study focusing on the more in-depth understanding of the patomechanism of migraine disorder. In the second part of my doctoral research, I developed a HILIC-MS/MS method for the analysis of anthranilic acid derivatives of oligosaccharides released from AGP. The method enabled the identificiation of the highest number of isomers ever detected in AGP, which is primarily due to the high resolution chromatographic method. The method was applied for the measurement of serum AGP obtained from 18 high-risk melanoma malignum patients and 19 healthy control individuals. I discovered how the disease affects the gylcosyaltion profile of AGP, and identified two triantennary (N5H6S2, N5H6S3F) and two tetraantennary (N6H7S2, N6H7S2F) oligosaccharides with their related variables being the most meaningful to differentiate between malignant and control samples. I verified that the glycosylation pattern of AGP can serve as a biomarker for high-risk malignant melanoma that is superior to S100B protein in terms of sensitivity and negative predictive value. Based on the results presented here, it can be stated that the set of analytical and chemometric methods developed and applied can serve as a basis of a future, effective diagnostic procedure for malignant melanoma.