@masterthesis{Tannhaeuser, type = {Bachelor Thesis}, author = {Tannh{\"a}user, Tristan}, title = {Methodenentwicklung zur Bestimmung des Serumspiegels und der Stabilit{\"a}t von Bupropion und Hydroxy-Bupropion mittels LCMS Orbitrap im Zuge des therapeutischen Drug Monitorings}, url = {http://nbn-resolving.de/urn:nbn:de:hbz:1383-opus4-17690}, school = {Hochschule Rhein-Waal}, pages = {82}, abstract = {Patients undergoing psychiatric treatment are typically treated with a variety of medications, the interactions of which and the resulting impact on the serum concentration levels of the drugs are unpredictable. Such interactions and the occurrence of side effects due to incorrect dosages are also known for the antidepressant bupropion, emphasizing the importance of therapeutic drug monitoring for this medication. Therefore, this study aimed to develop and validate a method for the determination of serum levels of bupropion and its pharmacologically active major metabolite, hydroxybupropion, using LC-MS. Additionally, due to the low stability of bupropion at room temperature, the influence of this factor on the routine measurements of bupropion patient samples in the laboratory of the LVR-Klinik Viersen pharmacy was also examined. Various bupropion solutions (dissolved in methanol or human albumin) were prepared for measurement. These solutions were analyzed using an LC-MS "Exactive Plus Orbitrap" with a biphenyl column as the stationary phase and various mobile phases differing in polarity to allow for the generation of a gradient. An electron spray ionization (ESI) method and an Orbitrap detector were used for quantifying the sample concentration. The measurement of a 0.1 ng/ml bupropion solution and a 0.5 ng/ml hydroxybupropion solution resulted in a signal-to-noise ratio in the mass spectrum that was well above the required 3:1 ratio for background noise subtraction. As the concentration was already below the required detection limit of 0.2 ng/ml for bupropion and 17 ng/ml for hydroxybupropion, no further steps were taken to determine the actual limit of detection for economic reasons since sufficient sensitivity of the LC-MS method was already demonstrated. The investigations into the recovery rate (WFR) and ion suppression showed that the applied sample preparation (protein precipitation with acetonitrile) did not lead to any relevant loss of content and that no interfering effects from other components of the sample matrix occurred during the measurement. The WFR was determined to be 100 ± 5\% for bupropion and 101 ± 4.8\% for hydroxybupropion. The examination of ion suppression resulted in a content deviation from the target value of 4 ± 0.2\% for bupropion and -9 ± 0.1\% for hydroxybupropion. The linearity of the method was confirmed by measuring a 5-point calibration with a correlation coefficient for the regression line of approximately 0.99 for both analytes. The precision and reproducibility of the method were also confirmed through the evaluation of in-day and day-to-day variation, with a coefficient of variation of <10 for all measurements conducted for both analytes. Thus, a reliable method for the determination of bupropion content using LC-MS was successfully developed and validated. By participating in proficiency testing programs, the method will be further validated and potentially certified in the future.}, language = {de} } @masterthesis{Torzewska, type = {Bachelor Thesis}, author = {Torzewska, Agata}, title = {Method development for quantification of prescription drugs Fluphenazine and Flupentixol in serum.}, url = {http://nbn-resolving.de/urn:nbn:de:hbz:1383-opus4-12715}, school = {Hochschule Rhein-Waal}, pages = {74}, abstract = {The LVR clinic in Viersen belongs to a group of nine psychiatric clinics in NRW, Germany. In the pharmacy laboratory, the therapeutic drug monitoring is offered for antiepileptic drugs (AED´s), neuroleptics and antidepressants. Fluphenazine and Flupentixol are used to relieve the symptoms of schizophrenia and other similar mental health problems. The purpose of this work is the development and validation of methods for quantitation of the neuroleptics Fluphenazine and Flupentixol, contained in human serum. Therapeutic drug monitoring (TDM) is very important for a patient-matched therapy. TDM is applied to handle and direct the pharmacotherapy because of the pharmacokinetic differences between different individuals. The developed methods should be afterwards introduced into the daily routine of the laboratory. The analytical device used for this purpose is a Liquid Chromatography with a Mass Spectrometer (LCMS), with a Biphenyl Accucore separation column which is also used for other neuroleptics quantised. For Fluphenazine, an already existing in the laboratory sample precipitation method was used. Also, an already applied for other similar neuroleptics LCMS method, called "Biphenyl03_new" (lasting for 11 minutes, with a high gradient between the elution agents) was taken on, and resulted in a good linearity. In case of Flupentixol, a completely new method had to be established, in order to achieve a baseline separation of cis-Z-Flupentixol and trans-E-Flupentixol. For the sample preparation, a solid phase extraction method was developed. The established methods were then applied for quantitation of patient samples, and the stability of the measurements was proved. Also, the accuracy and precision of obtained results was tested in the Proficiency Test. Limit of quantitation achieved for Fluphenazine was 0,5ng/ml, whereas for Flupentixol the LOQ was 0,25ng/ml. The Limit of detection found was 0,05ng/ml for both substances. The development was successful for both analytes and the established methods were integrated into the daily routine of the laboratory.}, language = {en} }