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Run Time (run + time)
Kinds of Run Time Selected AbstractsThe Impact of Imperfect Processes on Production Run TimesDECISION SCIENCES, Issue 4 2000Tonya Boone ABSTRACT This paper investigates the interaction between the economics of production and imperfections in the production process. Specifically, this paper is the first to devise a model in an attempt to provide managers with guidelines to choose the appropriate production run times to buffer against both the production of defective items and stoppages occurring due to machine breakdowns. In addition to providing several structural properties of the model, we show that a manager will always incur a cost penalty when (s)he uses the results of two oft-cited models-the EMQ (Economic Order/Manufacturing Quantity) and the NR-E (No-Resumption, Exponential machine breakdown)-to determine production run times. [source] Effects of phlebotomy on haemodynamic characteristics during exercise in Standardbred trotters with red cell hypervolaemiaEQUINE VETERINARY JOURNAL, Issue 4 2001P. FUNKQUIST Summary Five Standardbred trotters with red cell hypervolaemia (RCHV) were compared before and after removal of approximately 22% (36 ml/kg bwt) of the total blood volume in order to evaluate the haemodynamic responses, haemorheological alterations and oxygen transport during exercise to fatigue. Data were recorded during submaximal exercise at 4 different speeds on a treadmill and then during continued running at the highest speed step until fatigue. Oxygen uptake (V,O2), pulmonary artery pressure (PAP), systemic artery pressure (SAP), heart rate (HR), haematocrit and haemoglobin concentrations (Hb) were measured. Arteriovenous O2 content difference (C(a-v,)O2), pulmonary vascular resistance (PVR) and total systemic resistance (TSR) were calculated. Whole blood and plasma viscosity and erythrocyte aggregation tendency were determined with a rotational viscometer. Endoscopy was performed after exercise. ANOVA was used for statistical analysis. Phlebotomy resulted in a decrease in haematocrit and Hb during the course of exercise. Blood and plasma viscosity were lower and erythrocyte aggregation tendency was higher after phlebotomy. Throughout exercise, including submaximal work and continued running to fatigue, PAP, SAP, PVR, TSR and C(a-v,)O2 were lower after phlebotomy. HR was higher after phlebotomy during submaximal exercise. Oxygen delivery and VO2 were lower after phlebotomy in the period from submaximal exercise to fatigue. Run time to fatigue was shorter after phlebotomy. Four horses showed exercise-induced pulmonary haemorrhage (EIPH) before phlebotomy and the degree of bleeding was diminished but not abolished after phlebotomy. The reductions in PVR, TSR, PAP and SAP after phlebotomy were probably a result of reduced blood viscosity. In conclusion, although a 22% reduction in blood volume improved the haemodynamic and haemorheological parameters and the degree of EIPH, it was found that RCHV trotters have to rely on high oxygen delivery to the working muscles for maintenance of maximal performance. [source] A language to model animation out of behaviour-embedded graphical componentsCOMPUTER ANIMATION AND VIRTUAL WORLDS (PREV: JNL OF VISUALISATION & COMPUTER ANIMATION), Issue 3 2002Prabir K. Pal Abstract Almost all entities,animate or inanimate,that we see around us change with time. The changes are brought about by changes in the values of their attributes. By using a set of parameters to represent the variable attributes of an entity, and by suitably manipulating their values at run time, the behaviour of an entity can be broadly mimicked in animation. The majority of entities, however, are all too complex to animate directly. They are better described in terms of nested layers of smaller and simpler entities, which we call components. Each component is structurally and behaviourally complete and can be described independent of its application. In the present paper, we propose a scheme for 3D animation that broadly follows this line. The keystone of this scheme is a language, nicknamed ,V', which defines the structural and visual attributes of each component of the scene and associates a parameterized behaviour with it, if necessary, in the form of a program script. Thereafter, wherever such a component appears, it does so with a built-in behaviour, which can nevertheless be regulated by its higher-level component through its parameters. The advantage is that an entire animation can be modelled in a declarative fashion in terms of nested components with embedded behaviour. Besides, each component is easy to write, alter and reuse. The effort for development, debugging and maintenance of animation modelled in this way is much less as the concerns are almost always local. Copyright © 2002 John Wiley & Sons, Ltd. [source] Towards workflow simulation in service-oriented architecture: an event-based approachCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 4 2008Yanchong Zheng Abstract The emergence of service-oriented architecture (SOA) has brought about a loosely coupled computing environment that enables flexible integration and reuse of heterogeneous systems. On building a SOA for application systems, more and more research has been focused on service composition, in which workflow and simulation techniques have shown great potential. Simulation of services' interaction is important since the services ecosystem is dynamic and in continuous evolution. However, there is a lack in the research of services' simulation, especially models, methods and systems to support the simulation of interaction behavior of composite services. In this paper, an enhanced workflow simulation method with the support of interactive events mechanism is proposed to fulfill this requirement. At build time, we introduce an event sub-model in the workflow meta-model, and our simulation engine supports the event-based interaction pattern at run time. With an example simulated in the prototype system developed according to our method, the advantages of our method in model verification and QoS evaluation for service compositions are also highlighted. Copyright © 2007 John Wiley & Sons, Ltd. [source] Branch-and-Price Methods for Prescribing Profitable Upgrades of High-Technology Products with Stochastic Demands*DECISION SCIENCES, Issue 1 2004Purushothaman Damodaran ABSTRACT This paper develops a model that can be used as a decision support aid, helping manufacturers make profitable decisions in upgrading the features of a family of high-technology products over its life cycle. The model integrates various organizations in the enterprise: product design, marketing, manufacturing, production planning, and supply chain management. Customer demand is assumed random and this uncertainty is addressed using scenario analysis. A branch-and-price (B&P) solution approach is devised to optimize the stochastic problem effectively. Sets of random instances are generated to evaluate the effectiveness of our solution approach in comparison with that of commercial software on the basis of run time. Computational results indicate that our approach outperforms commercial software on all of our test problems and is capable of solving practical problems in reasonable run time. We present several examples to demonstrate how managers can use our models to answer "what if" questions. [source] An improved validated ultra high pressure liquid chromatography method for separation of tacrolimus impurities and its tautomersDRUG TESTING AND ANALYSIS, Issue 3 2010Acharya Subasranjan Abstract A selective, specific and sensitive ultra high pressure liquid chromatography (UHPLC) method was developed for determination of tacrolimus degradation products and tautomers in the preparation of pharmaceuticals. The chromatographic separation was performed on Waters ACQUITY UPLC system and BEH C8 column using gradient elution of mobile phase A (90:10 v/v of 0.1% v/v triflouroacetic acid solution and Acetonitrile) and mobile phase B (90:10 v/v acetonitrile and water) at a flow rate of 0.6 mL min,1. Ultraviolet detection was performed at 210 nm. Tacrolimus, tautomers and impurities were chromatographed with a total run time of 25 min. Calibration showed that the response of impurity was a linear function of concentration over the range 0.3,6 µg mL,1 (r2 , 0.999) and the method was validated over this range for precision, intermediate precision, accuracy, linearity and specificity. For precision study, percentage relative standard deviation of each impurity was < 15% (n = 6). The method was found to be precise, accurate, linear and specific. The proposed method was successfully employed for estimation of tacrolimus impurities in pharmaceutical preparations. Copyright © 2010 John Wiley & Sons, Ltd. [source] Validated capillary electrophoresis assay for the simultaneous enantioselective determination of propafenone and its major metabolites in biological samplesELECTROPHORESIS, Issue 8 2006Minoo Afshar Abstract A robust, inexpensive, and fully validated CE method for the simultaneous determination of the enantiomers of propafenone (PPF), 5-hydroxy-propafenone (5OH-PPF) and N -despropyl-propafenone (NOR-PPF) in serum and in in vitro media is described. It is based upon liquid,liquid extraction at alkaline pH followed by analysis of the reconstituted extract by CE in presence of a pH,2.0 running buffer composed of 100,mM sodium phosphate, 19% methanol, and 0.6% highly sulfated ,-CD. For each compound, the S -enantiomers are shown to migrate ahead of their antipodes, and the overall run time is about 30,min. Enantiomer levels between 25 and 1000,ng/mL provide linear calibration graphs, and the LOD for all enantiomers is between 10 and 12,ng/mL. The assay is shown to be suitable for the determination of the enantiomers of PPF and its metabolites in in vitro incubations comprising human liver microsomes or single CYP450 enzymes (SUPERSOMES). Incubations with CYP2D6 SUPERSOMES revealed, for the first time, the simultaneous formation of the enantiomers of 5OH-PPF and NOR-PPF with that enzyme. CE data can be used for the evaluation of the enzymatic N -dealkylation and hydroxylation rates. [source] Development of capillary zone electrophoresis-electrospray ionization-mass spectrometry for the determination of lamotrigine in human plasmaELECTROPHORESIS, Issue 13 2004Jack Zheng Abstract A method of coupling capillary zone electrophoresis (CZE) with electrospray ionization-mass spectrometry (ESI-MS) detection has been developed for monitoring an antiepileptic drug, lamotrigine (LTG) in human plasma. The CZE-MS was developed in three stages: (i) CZE separation and ESI-MS detection of LTG and tyramine (TRM, internal standard) were simultaneously optimized by studying the influence of CZE background electrolyte (BGE) pH, BGE ionic strength, and nebulizer pressure of the MS sprayer; (ii) sheath liquid parameters, such as pH, ionic strength, organic modifier content, and flow rate of the sheath liquid, were systematically varied under optimum CZE-MS conditions developed in the first stage; (iii) MS sprayer chamber parameters (drying gas temperature and drying gas flow rate) were varied for the best MS detection of LTG. The developed assay was finally applied for the determination of LTG in plasma samples. The linear range of LTG in plasma sample assay was between 0.1,5.0 ,g/mL with a limit of detection as low as 0.05 ,g/mL and run time less than 6 min. Finally, the concentration-time profile of LTG in human plasma sample was found to correlate well when CZE-ESI-MS was compared to a more established method of high-performance liquid chromatography with ultraviolet detection. [source] Investigation of a capillary electrophoretic approach for direct quantification of apolipoprotein A-I in serumELECTROPHORESIS, Issue 9 2003Rainer Lehmann Abstract In the present study a rapid, reproducible and robust capillary electrophoresis (CE) procedure for the quantification of apolipoprotein A-I (Apo A-I) in serum without pretreatment has been developed (total run time, 11 min). The coefficients of variation (CV; n = 10) for the relative peak area are 1.8% at a concentration of 145 mg/dL and 1.6% at 196 mg/dL; and for the inter-assay 8.9% at 161 mg/dL (10 consecutive days), i.e., similar to the CVs of a high-throughput immunonephelometric routine assay. The CV for the migration time is 0.4% (n = 20). The robustness of the CE approach was tested in patient samples with hemolysis, hyperbilirubinemia and hyperlipidemia. A comparison of 99 Apo A-I serum values with results of a fixed-time immunonephelometric routine assay showed a positive constant bias of 60% (mean) for the immunonephelometric values, no deviation from linearity, but significant deviations in several samples. Investigations on interferences in the CE analyses gave no evidence that CE failed. Our study shows that CE is amenable to a fast analysis and a reproducible and reliable quantification of Apo A-I level in sera of various clinical samples. [source] Parallel Delaunay mesh generation kernelINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 2 2003Nikos Chrisochoides Abstract We present the results of an evaluation study on the re-structuring of a latency-bound mesh generation algorithm into a latency-tolerant parallel kernel. We use concurrency at a fine-grain level to tolerate long, variable, and unpredictable latencies of remote data gather operations required for parallel guaranteed quality Delaunay triangulations. Our performance data from a 16 node SP2 and 32 node Cluster of Sparc Workstations suggest that more than 90% of the latency from remote data gather operations can be masked effectively at the cost of increasing communication overhead between 2 and 20% of the total run time. Despite the increase in the communication overhead the latency-tolerant mesh generation kernel we present in this paper can generate tetrahedral meshes for parallel field solvers eight to nine times faster than the traditional approach. Copyright © 2003 John Wiley & Sons, Ltd. [source] A perceptual quality model intended for adaptive VoIP applications,INTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 3 2006Christian Hoene Abstract Quality models predict the perceptual quality of services as they calculate subjective ratings from measured parameters. In this article, we present a new quality model that evaluates Voice over IP (VoIP) telephone calls. In addition to packet loss rate, coding mode and delay, it takes into account the impairments due to changes in the transmission configuration (e.g. switching the coding mode or re-scheduling the playout time). Moreover, this model can be used at run time to control the transmission of such calls. It is also computationally efficient and open source. To demonstrate the potential of our model, we apply it to select the ideal coding and packet rate in bandwidth-limited environments. Furthermore, we decide, based on model predictions, whether to delay the playout of speech frames after delay spikes. Delay spikes often occur after congestion and cause packets to arrive too late. We show a considerable improvement in perceptual speech quality if our model is applied to control VoIP transmissions. Copyright © 2005 John Wiley & Sons, Ltd. [source] Tree search algorithm for assigning cooperating UAVs to multiple tasksINTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONTROL, Issue 2 2008Steven J. Rasmussen Abstract This paper describes a tree search algorithm for assigning cooperating homogeneous uninhabited aerial vehicles to multiple tasks. The combinatorial optimization problem is posed in the form of a decision tree, the structure of which enforces the required group coordination and precedence for cooperatively performing the multiple tasks. For path planning, a Dubin's car model is used so that the vehicles' constraint, of minimum turning radius, is taken into account. Due to the prohibitive computational complexity of the problem, exhaustive enumeration of all the assignments encoded in the tree is not feasible. The proposed optimization algorithm is initialized by a best-first search and candidate optimal solutions serve as a monotonically decreasing upper bound for the assignment cost. Euclidean distances are used for estimating the path length encoded in branches of the tree that have not yet been evaluated by the computationally intensive Dubin's optimization subroutine. This provides a lower bound for the cost of unevaluated assignments. We apply these upper and lower bounding procedures iteratively on active subsets within the feasible set, enabling efficient pruning of the solution tree. Using Monte Carlo simulations, the performance of the search algorithm is analyzed for two different cost functions and different limits on the vehicles' minimum turn radius. It is shown that the selection of the cost function and the limit have a considerable effect on the level of cooperation between the vehicles. The proposed deterministic search method can be applied on line to different sized problems. For small-sized problems, it provides the optimal solution. For large-sized problems, it provides an immediate feasible solution that improves over the algorithm's run time. When the proposed method is applied off line, it can be used to obtain the optimal solution, which can be used to evaluate the performance of other sub-optimal search methods. Copyright © 2007 John Wiley & Sons, Ltd. [source] An improved direct labeling method for the max,flow min,cut computation in large hypergraphs and applicationsINTERNATIONAL TRANSACTIONS IN OPERATIONAL RESEARCH, Issue 1 2003Joachim Pistorius Algorithms described so far to solve the maximum flow problem on hypergraphs first necessitate the transformation of these hypergraphs into directed graphs. The resulting maximum flow problem is then solved by standard algorithms. This paper describes a new method that solves the maximum flow problem directly on hypergraphs, leading to both reduced run time and lower memory requirements. We compare our approach with a state,of,the,art algorithm that uses a transformation of the hypergraph into a directed graph and an augmenting path algorithm to compute the maximum flow on this directed graph: the run,time complexity as well as the memory space complexity are reduced by a constant factor. Experimental results on large hypergraphs from VLSI applications show that the run time is reduced, on average, by a factor approximately 2, while memory occupation is reduced, on average, by a factor of 10. This improvement is particularly interesting for very large instances, to be solved in practical applications. [source] A simple and rapid high-performance liquid chromatographic (HPLC) method for 5-fluorouracil (5-FU) assay in plasma and possible detection of patients with impaired dihydropyrimidine dehydrogenase (DPD) activityJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2004J. Ciccolini PharmD PhD Summary Background:, Dihydropyrimidine dehydrogenase (DPD) gene polymorphism may lead to severe toxicity with 5-fluorouracil (5-FU), a major anticancer drug extensively used in clinical oncology. Drug monitoring combined with early detection of patients at risk would enable timely dose adaptation so as to maintain drug concentrations within a therapeutic window. However, the best method to identify such patients remains to be determined. Objective:, The aim of this study was to develop a rapid and simple high-performance liquid chromatographic (HPLC) method for estimating uracil/dihydrouracil (U/UH2) ratio in plasma, as an index of DPD status, and for assaying 5-FU as part of drug level monitoring. Method:, Assay of 5-FU, and U/UH2 detection were performed on a HPLC system equipped with UV detector. Analytes were separated at room temperature using a 5 ,m particles, 25 cm RP-18 X-Terra column. The mobile-phase consisted of a KH2PO4 salt solution (0·05 m) + 0·1% triethylamine (TEA) pumped at 0·4 mL/min. Detection of 5-FU and 5-bromouracil were performed at 254 nm; U and UH2 elution was monitored at 210 nm. Results:, The method was sensitive and specific for assaying 5-FU within the 5,500 ng/mL concentration range, which covers exposure levels currently met in clinical practice. The method was simple, and relatively cheap, and rapid, with an analytical run time of about 30 min. Data from a patient with 5-FU toxicity suggest that the method was capable of identifying DPD metabolic phenotype in cancer patients, based on measurement of plasma U/UH2 ratio. Conclusion:, The method described should be suitable both for detecting patients at high risk of 5-FU toxicity, and for drug level monitoring during chemotherapy. [source] Error modeling and calibration of exteroceptive sensors for accurate mapping applicationsJOURNAL OF FIELD ROBOTICS (FORMERLY JOURNAL OF ROBOTIC SYSTEMS), Issue 1 2010James P. Underwood Reliable robotic perception and planning are critical to performing autonomous actions in uncertain, unstructured environments. In field robotic systems, automation is achieved by interpreting exteroceptive sensor information to infer something about the world. This is then mapped to provide a consistent spatial context, so that actions can be planned around the predicted future interaction of the robot and the world. The whole system is as reliable as the weakest link in this chain. In this paper, the term mapping is used broadly to describe the transformation of range-based exteroceptive sensor data (such as LIDAR or stereo vision) to a fixed navigation frame, so that it can be used to form an internal representation of the environment. The coordinate transformation from the sensor frame to the navigation frame is analyzed to produce a spatial error model that captures the dominant geometric and temporal sources of mapping error. This allows the mapping accuracy to be calculated at run time. A generic extrinsic calibration method for exteroceptive range-based sensors is then presented to determine the sensor location and orientation. This allows systematic errors in individual sensors to be minimized, and when multiple sensors are used, it minimizes the systematic contradiction between them to enable reliable multisensor data fusion. The mathematical derivations at the core of this model are not particularly novel or complicated, but the rigorous analysis and application to field robotics seems to be largely absent from the literature to date. The techniques in this paper are simple to implement, and they offer a significant improvement to the accuracy, precision, and integrity of mapped information. Consequently, they should be employed whenever maps are formed from range-based exteroceptive sensor data. © 2009 Wiley Periodicals, Inc. [source] Ticlopidine quantification in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry.JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 12 2004Application to bioequivalence study Abstract A rapid, sensitive and specific method to quantify ticlopidine in human plasma using clopidogrel as the internal standard (IS) is described. The analyte and the IS were extracted from acidified plasma by liquid,liquid extraction using diethyl ether,hexane (80 : 20, v/v). The extracts were analyzed by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC/MS/MS). Chromatography was performed isocratically on a Jones Genesis C8 4 µm analytical column (150 × 4.1 mm i.d.). The method had a chromatographic run time of 3.0 min and a linear calibration curve over the range 1.0,1000 ng ml,1 (r2 > 0.999427). The limit of quantification was 1.0 ng ml,1. This HPLC/MS/MS procedure was used to assess the bioequivalence of two ticlopidine 250 mg tablet formulations (ticlopidine test formulation from Apotex do Brasil, Brazil, and Ticlid from Sanofi-Synthelabo, standard reference formulation). A single 250 mg dose of each formulation was administered to healthy volunteers. The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for Cmax and area under the curve ratios were all inside the 80,125% interval proposed by the US Food and Drug Administration, it was concluded that ticlopidine formulation from Apotex do Brasil is bioequivalent to Ticlid formulation with respect to both the rate and the extent of absorption. Copyright © 2004 John Wiley & Sons, Ltd. [source] Development and validation of a method based on a QuEChERS procedure and heart-cutting GC-MS for determination of five mycotoxins in cereal productsJOURNAL OF SEPARATION SCIENCE, JSS, Issue 4-5 2010Sara C. Cunha Abstract A new analytical method for the rapid and simultaneous determination of five mycotoxins (zearelenone, deoxynivalenol, Fusarenon X, 15-acetyldeoxynivalenol and nivalenol) in breakfast cereals and flours by heart-cutting GC-MS has been developed and validated. Extraction was performed with MeCN, applying a modified QuEChERS (QUick, Easy, CHeap, Effective, Rugged and Safe) procedure, and the extracts were analyzed after a silylation of the analytes under study. Careful optimization of the parameters of Deans Switch device and GC-MS was achieved in order to attain a fast separation in SIM mode, allowing a total run time of only 8,min. Acceptable recoveries for all mycotoxins at two different spiking levels (20 and 100,,g/kg) were achieved with good repeatability (from 9 to 21%). LOD ranged from 2 to 15,,g/kg and LOQ ranged from 5 to 50,,g/kg, which were lower than the maximum limit legal established by the European Union (EU). The method developed was applied to commercial breakfast cereals and flours; among the mycotoxins studied, deoxynivalenol and zearalenone were the most predominant. [source] Automated determination of venlafaxine in human plasma by on-line SPE-LC-MS/MS.JOURNAL OF SEPARATION SCIENCE, JSS, Issue 4 2009Application to a bioequivalence study Abstract A new automated SPE-LC-ESI-MS/MS method was developed and validated to quantify venlafaxine in human plasma using fluoxetine as an internal standard. The analytes were automatically extracted from plasma by C18 SPE cartridges, separated on a C8 RP column and analyzed by MS in the multiple reaction-monitoring (MRM) mode. The method has a chromatographic run time of 4.0 min and a linear calibration curve over the range of 0.25,200 ng/mL (r >0.997). The between-run precisions, based on the percent RSD for replicate quality controls (0.75; 80, and 200 ng/mL), were < 8.5% for all concentrations. The between-run accuracies, based on the percent relative error, were < 4.0%. This method was successfully employed in a bioequivalence study of two venlafaxine capsule formulations (test formulation from Eurofarma (Brazil) and Efexor XR, reference formulation, from Wyeth-Whitehall, Brazil) in 48 healthy volunteers of both sexes who received a single 150 mg dose of each formulation. More than 3000 samples were analyzed eliminating the analyst's exposure to hazardous organic solvents normally employed in off-line liquid,liquid extractions. The 90% confidence interval (CI) of the individual ratio geometric mean for Test/Reference was 91.6,103.4% for AUC0,48 h and 102.2,112.6% for Cmax. Since both 90% CI for AUC0,48 h and Cmax were included in the 80,125% interval proposed by the US Food and Drug Administration (FDA) and the Brazilian National Health Surveillance Agency (ANVISA), the test formulation was considered bioequivalent to Efexor XR according to both the rate and extent of absorption. [source] Rapid simultaneous determination of codeine and morphine in plasma using LC-ESI-MS/MS: Application to a clinical pharmacokinetic studyJOURNAL OF SEPARATION SCIENCE, JSS, Issue 2 2009Qiongfeng Liao Abstract A rapid and sensitive high-performance LC-MS/MS method was developed and validated for the simultaneous quantification of codeine and its metabolite morphine in human plasma using donepezil as an internal standard (IS). Following a single liquid-liquid extraction with ethyl acetate, the analytes were separated using an isocratic mobile phase on a C18 column and analyzed by MS/MS in the selected reaction monitoring mode using the respective [M+H]+ ions, mass-to-charge ratio (m/z) 300/165 for codeine, m/z 286/165 for morphine and m/z 380/91 for IS. The method exhibited a linear dynamic range of 0.2,100/0.5,250 ng/mL for codeine/morphine in human plasma, respectively. The lower LOQs were 0.2 and 0.5 ng/mL for codeine and its metabolite morphine using 0.5 mL of human plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.0 min for each sample made it possible to analyze more than 300 human plasma samples per day. The validated LC-MS/MS method was applied to a pharmacokinetic study in which healthy Chinese volunteers each received a single oral dose of 30 mg codeine phosphate. [source] Evaluation of mobile phase, ion pairing, and temperature influence on an HILIC-MS/MS method for L -arginine and its dimethylated derivatives detectionJOURNAL OF SEPARATION SCIENCE, JSS, Issue 13 2008Giuseppe Paglia Abstract Asymmetric NG,,NG -dimethylarginine (ADMA) increases in diseases such as renal failure, diabetes mellitus, and hypercholesterolemia. The feasibility and utility of a hydrophilic interaction chromatography (HILIC) method for the separation of free L -arginine (Arg), ADMA, and symmetric NG,,NG, -dimethylarginine (SDMA) on a typical silica column were explored and the impact of some experimental parameters on the chromatographic behavior of these analytes was investigated. The effect of water and TFA content in mobile phase and of column temperature was investigated during the development of a fast and simple HILIC-MS/MS method that might be suitable for the quantification of free Arg, ADMA, and SDMA in plasma for routine analysis. Our results show that a good compromise between efficiency and peak shape with acceptable retention and total chromatographic run time is achieved using an ACN/water (90:10) mobile phase with TFA% as additive ranging from 0.015 to 0.025% and column temperature ranging from 25 to 30°C. [source] Quantification of alkylresorcinols in human plasma by liquid chromatography/tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 5 2010Alastair B. Ross Alkylresorcinols (AR) are of interest as biomarkers of wholegrain wheat and rye intake in epidemiological studies and are currently mainly measured by gas chromatography/mass spectrometry (GC/MS) after labour-intensive sample preparation including liquid-liquid extraction, solid-phase extraction (SPE) and chemical derivatization. This manuscript describes and validates an alternative approach based on normal-phase liquid chromatography/tandem mass spectrometry for the quantification of alkylresorcinols in human plasma. The method requires neither SPE nor chemical derivatization and has a shortened run time compared to GC/MS. Normal- and reversed-phase columns and various mobile phases were evaluated with and without previous SPE of the samples. Normal-phase chromatography allowed separation of AR from the interfering triacylglycerols, diacylglycerols and sterols and enabled detection of AR even without SPE of the samples. The described method has instrumental lower limits of detection in the 25,75 pg range, and lower limits of quantification in the 75,250 pg range. Pooled human plasma and 2H4 -nonadecylresorcinol (internal standard) was applied to calibrate the method in the 20,12,000,nM range. The overall method showed intra-batch precision of 8.6% and an averaged accuracy of 100.2%. Applications for diverse human plasma samples are presented and are compared with the results determined by GC/MS. Based on the presented data; this method requiring less sample preparation is suggested for further evaluation as an alternative to GC/MS for analysis of biomarkers of wholegrain wheat and rye intake in epidemiological studies. Copyright © 2010 John Wiley & Sons, Ltd. [source] Rapid and sensitive on-line liquid chromatographic/tandem mass spectrometric determination of an ethylene oxide-DNA adduct, N7-(2-hydroxyethyl)guanine, in urine of nonsmokersRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 5 2008Chih-Chun Jean Huang Ethylene oxide (EtO) is classified as a known human carcinogen. The formation of EtO-DNA adducts is considered as an important early event in the EtO carcinogenic process. An isotope-dilution on-line solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry method was then developed to analyze one of the EtO-DNA adducts, N7-(2-hydroxyethyl)guanine (N7-HEG), in urine of 46 nonsmokers with excellent accuracy, sensitivity and specificity. The merits of this method include small sample volume (only 120,µL urine required), automated sample cleanup, and short total run time (12 minutes per sample). This method demonstrates its high-throughput capacity for future molecular epidemiology studies on the potential health effects resulting from the low-dose EtO exposure. Copyright © 2008 John Wiley & Sons, Ltd. [source] Determination of levetiracetam in human plasma by liquid chromatography/electrospray tandem mass spectrometry and its application to bioequivalence studiesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2006Deepak S. Jain The first liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the determination of levetiracetam, an antiepileptic drug, in human plasma is described. The plasma filtrate obtained after solid-phase extraction (SPE), using a polymer-based, hydrophilic-lipophilic balanced (HLB) cartridge, was submitted directly to a short column LC/MS/MS assay. There was no significant matrix effect on the analysis. For validation of the method, the recovery of the free analytes was compared to that from an optimized extraction method, and the analyte stability was examined under conditions mimicking sample storage, handling, and analytical procedures. The extraction procedure yielded extremely clean extracts with a recovery of 79.95% and 89.02% for levetiracetam and the internal standard (IS), respectively. The intra-assay and inter-assay precision for the samples at the lower limit of quantitation (LLOQ) were 6.33 and 6.82%, respectively. The calibration curves were linear for the dynamic range of 0.5 to 50,µg/mL with a correlation coefficient r,,,0.9971. The intra-assay accuracy at LLOQ, LQC, MQC, and HQC levels ranged from 81.60 to 95.40, 93.00 to 103.47, 95.97 to 104.09, and 91.15 to 95.18%, respectively, while the inter-assay accuracy at LLOQ, LQC, MQC and HQC levels varied from 80.20 to 95.40, 88.53 to 107.53, 95.97 to 108.45, and 91.15 to 112.70%, respectively. The method is rugged and fast with a total instrumental run time of 2,min. The method was successfully applied for bioequivalence studies in human subject samples after oral administration of 1000,mg immediate release (IR) formulations. Copyright © 2006 John Wiley & Sons, Ltd. [source] Liquid chromatography/tandem triple-quadrupole mass spectrometry for determination of paclitaxel in rat tissuesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2006Xinyong Tong A liquid chromatography/tandem triple-quadrupole mass spectrometry assay to quantify paclitaxel in rat tissue homogenates containing taxol or paclitaxel nanoliposome (PTX-NLP) was developed and validated. Liquid-liquid extraction with tert -butyl methyl ether was used for tissue sample preparation and docetaxel was used as the internal standard. Paclitaxel and docetaxel were separated on a 200,mm,×,4.6,mm,×,5,µm C18 column and quantified using a triple-quadrupole mass spectrometer operating in positive ion electrospray selective reaction monitoring mode (ESI+ -SRM) with a total run time of 6.0,min. The peak area of the m/z 876.3,,,307.9 transition of paclitaxel is measured versus that of the m/z 830.3,,,549.1 transition of docetaxel to generate the standard curves. The standard curves were linear over the concentration range of 0.2008,2008,ng/mL for different tissues. The method had high extraction recovery (>90%) and accuracy (>90%) with the intra-day and inter-day precision <15%. Frozen stability, freeze/thaw stability, extraction stability and solution stability at ambient temperature were examined, which indicated the tissue samples should be extracted within 5 days and avoid being frozen and thawed repeatedly over 5 times. Extracted samples after evaporation could be stored at ,20°C for 20 days without drug degradation and no degradation was also observed after solution samples were left to stand at ambient temperature for 24,h. This assay was used to support an in vivo biodistribution study of PTX-NLP in rats. Copyright © 2006 John Wiley & Sons, Ltd. [source] Increased productivity in quantitative bioanalysis using a monolithic column coupled with high-flow direct-injection liquid chromatography/tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 11 2006Mike-Qingtao Huang The feasibility of using a monolithic column as the analytical column in conjunction with high-flow direct-injection liquid chromatography/tandem mass spectrometry (LC/MS/MS) to increase productivity for quantitative bioanalysis has been investigated using plasma samples containing a drug and its epimer metabolite. Since the chosen drug and its epimer metabolite have the same selected reaction monitoring (SRM) transitions, chromatographic baseline separation of these two compounds was required. The results obtained from this monolithic column system were directly compared with the results obtained from a previously validated assay using a conventional C18 column as the analytical column. Both systems have the same sample preparation, mobile phases and MS conditions. The eluting flow rate for the monolithic column system was 3.2,mL/min (with 4:1 splitting) and for the C18 column system was 1.2,mL/min (with 3:1 splitting). The monolithic column system had a run time of 5,min and the conventional C18 column system had a run time of 10,min. The methods on the two systems were found to be equivalent in terms of accuracy, precision, sensitivity and chromatographic separation. Without sacrificing the chromatographic separation, sensitivity, accuracy and precision of the method, the reduced run time of the monolithic column method increased the sample throughput by a factor of two. Copyright © 2006 John Wiley & Sons, Ltd. [source] A novel on-line solid-phase extraction approach integrated with a monolithic column and tandem mass spectrometry for direct plasma analysis of multiple drugs and metabolitesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 22 2005Xu Zang An on-line solid-phase extraction liquid chromatography/tandem mass spectrometry (SPE LC/MS/MS) assay using a newly developed SPE column and a monolithic column was developed and validated for direct analysis of plasma samples containing multiple analytes. This assay was developed in an effort to increase bioanalysis throughput and reduce the complexity of on-line SPE LC/MS/MS systems. A simple column-switching configuration that requires only one six-port valve and one HPLC pumping system was employed for on-line plasma sample preparation and subsequent gradient chromatographic separation. The resulting analytical method couples the desired sensitivity with ease of use. The method was found to perform satisfactorily for direct plasma analysis with respect to assay linearity, specificity, sensitivity, precision, accuracy, carryover, and short-term stability of an eight-analyte mixture in plasma. A gradient LC condition was applied to separate the eight analytes that cannot be distinctly differentiated by MS/MS. With a run time for every injection of 2.8,min, a minimum of 300 direct plasma injections were made on one on-line SPE column without noticeable changes in system performance. Due to the ruggedness and simplicity of this system, generic methods can be easily developed and applied to analyze a wide variety of compounds in a high-throughput manner without laborious off-line sample preparation. Copyright © 2005 John Wiley & Sons, Ltd. [source] Liquid chromatography/tandem mass spectrometric quantification with metabolite screening as a strategy to enhance the early drug discovery processRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2002Philip R. Tiller Throughput for early discovery drug metabolism studies can be increased with the concomitant acquisition of metabolite screening information and quantitative analysis using ultra-fast gradient chromatographic methods. Typical ultra-fast high-performance liquid chromatography (HPLC) parameters used during early discovery pharmacokinetic (PK) studies, for example, employ full-linear gradients over 1,2,min at very high flow rates (1.5,2,mL/min) on very short HPLC columns (2,×,20,mm). These conditions increase sample throughput by reducing analytical run time without sacrificing chromatographic integrity and may be used to analyze samples generated from a variety of in vitro and in vivo studies. This approach allows acquisition of more information about a lead candidate while maintaining rapid analytical turn-around time. Some examples of this approach are discussed in further detail. Copyright © 2002 John Wiley & Sons, Ltd. [source] Quantitative screening and matrix effect studies of drug discovery compounds in monkey plasma using fast-gradient liquid chromatography/tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2001Yunsheng Hsieh A higher-throughput bioanalytical method based on fast-gradient (1,min run time) high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometry (MS/MS) was developed for screen-type analyses of plasma samples from early drug discovery studies in support of exploratory pharmacodynamic studies. The HPLC system equipped with minibore column was interfaced with either atmospheric pressure chemical ionization (APCI) or electrospray (ESI) ionization techniques. The matrix ion suppression effect of both quantitative HPLC/MS/MS analyses was compared using the post-column infusion system. The use of the described methods provided advantages such as a shorter chromatographic region of ion suppression, less solvent consumption and shorter run times in comparison with standard analytical column HPLC/MS/MS methods. The analytical results obtained by both HPLC/MS/MS methods were in good agreement (within 15% of error) and displayed a good correlation with the pharmacodynamic outcome. Copyright © 2001 John Wiley & Sons, Ltd. [source] Autoindexing the diffraction patterns from crystals with a pseudotranslationACTA CRYSTALLOGRAPHICA SECTION D, Issue 6 2009Nicholas K. Sauter Rotation photographs can be readily indexed if enough candidate Bragg spots are identified to properly sample the reciprocal lattice. However, while automatic indexing algorithms are widely used for macromolecular data processing, they can produce incorrect results in special situations where a subset of Bragg spots is systematically overlooked. This is a potential outcome in cases where a noncrystallographic translational symmetry operator closely mimics an exact crystallographic translation. In these cases, a visual inspection of the diffraction image will reveal alternating strong and weak reflections. However, reliable detection of the weak-intensity reflections by software requires a systematic search for a diffraction signal targeted at specific reciprocal-space locations calculated a priori by considering all possible pseudotranslations. Care must be exercised to distinguish between true lattice diffraction and spurious signals contributed by neighboring overlapping Bragg spots, non-Bragg diffraction and noise. Such procedures have been implemented within the autoindexing program LABELIT and applied to known cases from publicly available data sets. Routine use of this type of signal search adds only a few seconds to the typical run time for autoindexing. The program can be downloaded from http://cci.lbl.gov/labelit. [source] Simultaneous determination of lamivudine, stavudine and nevirapine in human plasma by LC,MS/MS and its application to pharmacokinetic study in clinicBIOMEDICAL CHROMATOGRAPHY, Issue 9 2010Zhou Li Abstract A new high-throughput LC,MS/MS method for the simultaneous determination of lamivudine (3TC), stavudine (d4T) and nevirapine (NVP) in human plasma is presented, with zidovudine as an internal standard. The analytes were extracted from plasma by protein precipitation and only 150,,L plasma was needed. Chromatographic separation was achieved on a Shiseido C8 column (150 × 2.0,mm, 5,,m) with a total run time of 6,min. A tandem mass spectrometric detection was conducted using multiple reaction monitoring under positive ionization mode with an electrospray ionization interface. The method was developed and validated over the concentration range of 25,5000,ng/mL for 3TC and NVP and 20,4000,ng/mL for d4T. The method was validated in terms of intra- and inter-day precision (,8.6%), accuracy (within ± 8.4%), linearity and specificity. The method has been successfully applied to the pharmacokinetic study of a combination treatment of 300,mg lamivudine, 30,mg stavudine and 200,mg nevirapine in 22 healthy male volunteers under fasting conditions. Copyright © 2010 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||