Validering av en UPLC-MSMS metode for kvantifisering av antidepressiva, antipsykotika og antiarytmika i serum

Det har blitt undersøkt om ett analyseprogram på UPLC-MSMS kan erstatte dagens to analyseprogram for kvantifisering av antidepressiva (fluoksetin, sertralin og vortioksetin), antipsykotika (aripiprazol og klorprotiksen), antiarytmika (flekainid) og metabolittene (norfluoksetin og dehydroaripiprazol) i serum på UPLC-MSMS. Videreutvikling av metoden har gjort det mulig å effektivisere laboratoriedriften. Grunnlaget for å validere den nye metoden var basert på bestemmelse av repeterbarhet, reproduserbarhet, riktighet, deteksjonsgrense og nedre kvantifiseringsgrense, linearitet og selektivitet for målanalytter i kvalitetskontroller og standarder. I tillegg ble det utført samkjøring med to instrumenter ved bruk av kontroller og pasientprøver. Analysedriften ble undersøkt for vurdering av metodens robusthet. Resultatene viste at repeterbarheten var innenfor kravet på %CV ≤ 10% og reproduserbarheten innenfor kravet på %CV ≤ 15%. Riktigheten med akseptabel %bias på ≤ 15% ble innfridd for alle analytter og alle Z-verdier for SLP-prøvene var innenfor |Z| ≤ 2. Metoden viste akseptabel linearitet i og over måleområdet, hvor alle analyttene innfridde kravet R ≥ 0,9850. Linearitetsundersøkelsen tilfredsstilte kriterier for riktighet og presisjon, og residualer for standardkurvene viste ingen trender. Undersøkelse av nedre kvantifiseringsgrense viste at alle analytter har et signal til støy-forhold (S/N) >30 for kvantifiseringsion, og S/N-forhold >10 for kvalifiseringsion, og tilfredsstilte kriterier for presisjon og riktighet ved nedre kvantifiseringsgrense. Metoden viste akseptabel selektivitet da det ikke var funn av interfererende topper i kromatogram for blankprøver. Samkjøring av prøver på to instrumenter viste resultater med %differanse innenfor kravet ≤ 20%, med unntak av dehydroaripiprazol. Det ble vurdert at %differansen ikke hadde medisinsk betydning, og samkjøringen ble godkjent. Metodens robusthet viste resultater som tilfredsstilte lav drift i analyseserien. Valideringsparameterne som er blitt undersøkt indikerer at ett analyseprogram kan erstatte to analyseprogram på UPLC-MSMS. Videre arbeid innebærer at metoden valideres videre ved undersøkelse av blant annet valideringsparameterne stabilitet av retensjonstid og ioner, og fortynning av prøver.It has been examined whether one analysis program on UPLC-MSMS can replace the current two analysis programs for quantification of antidepressants (fluoxetine, sertraline and vortioxetine), antipsychotics (aripiprazole and chlorprotixene), antiarrhythmics (flecainide) and the metabolites (norfluoxetine and dehydroaripiprazole) in serum on UPLC-MSMS. Further development of the method has made it possible to make daily laboratory operations more effective. The validation of the new method was based on the determination of repeatability, reproducibility, accuracy, detection limit and lower limit of quantification, linearity and selectivity for the analytes in quality controls and standards. In addition, a comparison of measurements on two instruments, a co-run, was performed using quality controls and patient samples. The analysis drift was investigated to assess the robustness of the method. The results showed that the repeatability was within the requirement of %CV ≤ 10% and the reproducibility within the requirement of %CV ≤ 15%. The accuracy with an acceptable %bias of ≤ 15% was met for all analytes and all Z-values for the SLP samples were within |Z| ≤ 2. The method showed acceptable linearity in and above the measurement range, where all of the analytes met the requirement R ≥ 0,9850. The linearity study fulfilled criteria for accuracy and precision, and residuals for the standard curves showed no trends. Examination of the lower limit of quantification showed that all analytes have a signal to noise ratio (S/N) >30 for quantification ion, and S/N ratio >10 for qualification ion, and met criteria for precision and accuracy at the lower limit of quantification. The method showed acceptable selectivity as no interfering peaks were found in the chromatogram for blank samples. The co-run of samples on two instruments showed results with a %difference within the requirement ≤ 20%, with the exception of dehydroaripiprazole. It was considered that the %difference had no medical significance, and the co-run was approved. The robustness of the method showed results that satisfied low drift in the analysis series. The validation parameters that have been investigated indicate that one analysis program can replace two analysis programs on UPLC-MSMS. Further work involves additional validation of the method by investigating the validation parameters including stability of retention time and ions, and dilution of samples

An overview of the Marine Systems Simulator (MSS): A simulink toolbox for marine control systems

The Marine Systems Simulator (MSS) is an environment which provides the necessary resources for rapid implementation of mathematical models of marine systems with focus on control system design. The simulator targets models¡Xand provides examples ready to simulate¡Xof different floating structures and its systems performing various operations. The platform adopted for the development of MSS is Matlab/Simulink. This allows a modular simulator structure, and the possibility of distributed development. Openness and modularity of software components have been the prioritized design principles, which enables a systematic reuse of knowledge and results in efficient tools for research and education. This paper provides an overview of the structure of the MSS, its features, current accessability, and plans for future development

Time- vs. Frequency-domain Identification of Parametric Radiation Force Models for Marine Structures at Zero Speed

The dynamics describing the motion response of a marine structure in waves can be represented within a linear framework by the Cummins Equation. This equation contains a convolution term that represents the component of the radiation forces associated with fluid memory effects. Several methods have been proposed in the literature for the identification of parametric models to approximate and replace this convolution term. This replacement can facilitate the model implementation in simulators and the analysis of motion control designs. Some of the reported identification methods consider the problem in the time domain while other methods consider the problem in the frequency domain. This paper compares the application of these identification methods. The comparison is based not only on the quality of the estimated models, but also on the ease of implementation, ease of use, and the flexibility of the identification method to incorporate prior information related to the model being identified. To illustrate the main points arising from the comparison, a particular example based on the coupled vertical motion of a modern containership vessel is presented