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Mean Accuracy (mean + accuracy)
Selected AbstractsSimultaneous quantification of cyclophosphamide, 4-hydroxycyclophosphamide, N,N,,N, -triethylenethiophosphoramide (thiotepa) and N,N,,N, -triethylenephosphoramide (tepa) in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 3 2004Milly E. de Jonge Abstract The alkylating agents cyclophosphamide (CP) and N, N,, N, -triethylenethiophosphoramide (thiotepa) are often co-administered in high-dose chemotherapy regimens. Since these regimens can be complicated by the occurrence of severe and sometimes life-threatening toxicities, pharmacokinetically guided administration of these compounds, to reduce variability in exposure, may lead to improved tolerability. For rapid dose adaptations during a chemotherapy course, we have developed and validated an assay, using liquid chromatography coupled with electrospray tandem mass spectrometry (LC/MS/MS), for the routine quantification of CP, thiotepa and their respective active metabolites 4-hydroxycyclophosphamide (4OHCP) and N, N,, N, -triethylenephosphoramide (tepa) in plasma. Because of the instability of 4OHCP in plasma, the compound is derivatized with semicarbazide (SCZ) immediately after sample collection and quantified as 4OHCP-SCZ. Sample pretreatment consisted of protein precipitation with a mixture of methanol and acetronitrile using 100 µl of plasma. Chromatographic separation was performed on an Zorbax Extend C18 column (150 × 2.1 mm i.d., particle size 5 µm), with a quick gradient using 1 mM ammonia solution and acetonitrile, at a flow-rate of 0.4 ml min,1. The analytical run time was 10 min. The triple quadrupole mass spectrometer was operating in the positive ion mode and multiple reaction monitoring was used for drug quantification. The method was validated over the concentration ranges 200,40 000 ng ml,1 for CP, 50,5000 ng ml,1 for 4OHCP-SCZ and 5,2500 ng ml,1 for thiotepa and tepa, using 100 µl of human plasma. These dynamic concentration ranges proved to be relevant in daily practice. Hexamethylphosphoramide was used as an internal standard. The coefficients of variation were <12% for both intra-day and inter-day precisions for each compound. Mean accuracies were also between the designated limits (±15%). This robust and rapid LC/MS/MS assay is now successfully applied for routine therapeutic drug monitoring of CP, thiotepa and their metabolites in our hospital. Copyright © 2004 John Wiley & Sons, Ltd. [source] Biochemical and analytical development of the CIME cocktail for drug fate assessment in humansRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 16 2010Orianne Videau Phenotyping based on drug metabolism activity appears to be informative regarding mechanism-based interactions during drug development. We report here the first steps of the development of the innovative CIME cocktail. This cocktail is designed not only for the major cytochrome P450, with caffeine, amodiaquine, tolbutamide, omeprazole, dextromethorphan and midazolam as substrates of CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A, respectively, but also phase II enzymes UGT 1A1/6/9 with acetaminophen, P-gp and OATP1B1 with digoxin and rosuvastatin, and renal function with memantine. An assay combining ultra-performance liquid chromatography using a 1.7,µm particle size column with tandem mass spectrometry (UPLC/MS/MS) was set up for the simultaneous quantification of the 20 substrates and metabolites after extraction from human plasma using solid-phase extraction. The method was validated in the spirit of the FDA guidelines. Mean accuracy ranged from 87.7 to 115%, the coefficient of variance (CV%) of intra- and inter-run from 1.7 to 16.4% and from 1.6 to 14.9%, respectively, and for the limit of quantification (LOQ) with ten lots of plasma, accuracy ranged from 84 to 115% and CV% precision was <16%. Short-term stability was evaluated in eluate (4,h, room temperature), plasma (24,h, room temperature), the autosampler (24,h, 4°C) and in three freeze/thaw cycles in plasma. All except three analytes were stable under these conditions. For the three others a specific process can be followed. This robust, fast and sensitive assay in human plasma provides an analytical tool for ten-probe drugs of the CIME cocktail. Clinical samples will be assayed in the near future using this new assay method. Copyright © 2010 John Wiley & Sons, Ltd. [source] Digital soil mapping using artificial neural networksJOURNAL OF PLANT NUTRITION AND SOIL SCIENCE, Issue 1 2005Thorsten Behrens Abstract In the context of a growing demand of high-resolution spatial soil information for environmental planning and modeling, fast and accurate prediction methods are needed to provide high-quality digital soil maps. Thus, this study focuses on the development of a methodology based on artificial neural networks (ANN) that is able to spatially predict soil units. Within a test area in Rhineland-Palatinate (Germany), covering an area of about 600 km2, a digital soil map was predicted. Based on feed-forward ANN with the resilient backpropagation learning algorithm, the optimal network topology was determined with one hidden layer and 15 to 30 cells depending on the soil unit to be predicted. To describe the occurrence of a soil unit and to train the ANN, 69 different terrain attributes, 53 geologic-petrographic units, and 3 types of land use were extracted from existing maps and databases. 80% of the predicted soil units (n = 33) showed training errors (mean square error) of the ANN below 0.1, 43% were even below 0.05. Validation returned a mean accuracy of over 92% for the trained network outputs. Altogether, the presented methodology based on ANN and an extended digital terrain-analysis approach is time-saving and cost effective and provides remarkable results. Digitale Bodenkartierung mithilfe von Künstlichen Neuronalen Netzen Vor dem Hintergrund einer steigenden Nachfrage nach hoch auflösenden bodenkundlichen Flächeninformationen für die Umweltplanung und Modellierung werden schnelle und genaue Vorhersagemodelle benötigt, um hochqualitative Bodenprognosekarten zur Verfügung stellen zu können. Kernpunkt der hier vorgestellten Untersuchung ist daher die Entwicklung einer Methodik zur Erstellung von Bodenprognosekarten auf der Grundlage Künstlicher Neuronaler Netze (KNN). Als Untersuchungsgebiet diente eine Fläche von über 600 km2 im Pfälzer Wald. Vorwärts propagierende KNN auf Basis des "Resilent Backpropagation"-Algorithmus mit einer verdeckten Schicht aus 15 bis 30 Zellen erwiesen sich als optimal für die Prognose von Bodenformengesellschaften. Um das Auftreten einer Bodenformengesellschaft zu beschreiben und die KNN zu trainieren, wurden 69 Reliefparameter, 3 Nutzungsklassen sowie 53 geologisch-petrographische Einheiten verwendet. 80,% der vorhergesagten Bodenformengesellschaften (n = 33) zeigten Trainingsfehler (mittlerer quadratischer Fehler der KNN) von unter 0,1; 43,% sogar von unter 0,05. Die Validierung ergab Genauigkeiten in dem kartierten Gesamtraum von durchschnittlich über 92,% für die prognostizierten Bodenformengesellschaften. Zusammenfassend kann festgehalten werden, dass die vorgestellte Methodik auf der Basis von KNN und einer umfangreichen Digitalen Reliefanalyse einen zeit- und kosteneffektiven Ansatz zur Prognose von Bodenkarten darstellt, der hervorragende Ergebnisse liefern kann. [source] Simultaneous quantitative determination of cyclosporine A and its three main metabolites (AM1, AM4N and AM9) in human blood by liquid chromatography/mass spectrometry using a rapid sample processing methodRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 5 2006Nozomu Koseki We have developed a sensitive and specific liquid chromatography/mass spectrometry (LC/MS) method for the simultaneous determination of cyclosporine A (CsA) and its three main metabolites (AM1, AM4N and AM9) in human blood. Following protein precipitation, supernatant was directly injected into the LC/MS system. Chromatographic separation was accomplished on a Symmetry C8 (4.6,×,75,mm, 3.5,µm) column with a linear gradient elution prior to detection by atmospheric pressure chemical ionization (APCI) MS using selected ion monitoring (SIM) in positive mode. This method can be applied to single mass equipment. The analytical range for each analyte was set at 1,2500,ng/mL using 100,µL of blood sample. The analytical method was fully validated according to FDA guidance. Intra-day mean accuracy and precision were 95.2,113.5% and 0.9,8.9%, respectively. Inter-day mean accuracy and precision were 95.8,107.0% and 1.5,10.7%, respectively. In blood all analytes were stable during three freeze/thaw cycles, for 24,h at room temperature and for 12 months at or below ,15°C. Stability was also confirmed in processed samples for 24,h at 10°C and for 6 months at 4°C in methanol. In addition, we confirmed the method could avoid matrix effects from transplant subjects' samples. This LC/MS technique provided an excellent method for simultaneous quantitative determination of CsA and its three metabolites for evaluation of their pharmacokinetic profiles. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||