An automated sensor system for the continuous and in-line measurement of hydrogen peroxide in industrial applications is described. The hydrogen peroxide concentration can be measured over the entire pH range, over a wide concentration range of hydrogen peroxide (10(-3) 70 g/l), from 0 to 70( degrees )C, and with high precision and accuracy (errors less than 1% ). The system consists of a bypass in which the necessary electrodes are positioned and electronically controlled. The sensor is very selective for hydrogen peroxide, easy to instal, and it is stable for at least two months after calibration. The calibration can be done in the process solution during a running process.
A spectrometric method for the determination of L-carnitine has been developed based on the reaction of the 5,5' dithiobis-(2-nitrobenzoic) acid (DTNB) and adapted to a Technicon RA-2000 automatic analyser Química Farmacéutica Bayer, S.A.). The detection limit of the method is 13.2 mumol/l, with a measurement interval ranging from 30 to 320 mumoll1. Imprecision and accuracy are good even at levels close to the detection limit (coeffcient of variation of 5.4% for within-run imprecision for a concentration of 35 mumol/l). A good correlation was observed between the method studied and the radiometric method. The method evaluated has suffcient analytical sensitivity to diagnose carnitine deficiencies. The short time period required for sample processing (30 samples in 40min), the simple methodology and apparatus, the ease of personnel training and the low cost of the reagents make this method a good alternative to the classical radiometric method for evaluating serum L-carnitine in clinical laboratories without radioactive installations.
Significant opportunities and challenges are presented when transitioning from managing laboratory automation development of pharmaceutical products at a single site to collaborative management with multiple domestic and international sites. Prior to integrating Glaxo and Burroughs Wellcome about two years ago, each company had expertise in laboratory automation, but neither had a strategy for consistent business-justified laboratory automation. The approach for international harmonization of automation development of pharmaceutical test methods that the integrated company has adopted is presented. Some items to consider before undertaking a company-wide automation development harmonization programme are offered for consideration. Experiences encountered and future planned benefits are discussed.
Simultaneous spectrophotometric determination of Mn, Zn and Co was studied by two methods, classical partial least-squares (PLS) and kernel partial least-squares (KPLS), with 2-(5-bromo-2- pyridylazo)-5-diethylaminephenol (5-Br-PADAP) and cetyl pyridinium bromide (CPB). Two programs, SPGRPLS and SPGRKPLS, were designed to perform the calculations. Eight error functions were calculated for deducing the number of factors. Data reductions were performed using principle component analysis. The KPLS method was applied for the rapid determination from a data matrix with many wavelengths and fewer numbers of samples. The relative standard errors of prediction (RSEP) for all components with KPLS and PLS methods were the same (0.0247). Experimental results showed both methods to be successful even where there was severe overlap of spectra.
in Boston, USA.State-of-the-art developments in laboratory automation and robotics were reflected in the symposium programme, which included papers and posters on all aspects of the technology--drug discovery research, data handling and data management, chemical analysis, re-engineering the laboratory, laboratory workstations, bioanalytical assays, managing laboratory automation, dissolution testing, pharmaceutical analysis, automation and combinatorial chem- istry, validating automated methods and advanced topics.We are printing abstracts of papers from ISLAR and we hope that you find them informative and productive.The 1998 ISLAR will be held in Boston, USA from 18-21 October 1998.Session topics will be similar to previous years, but will also include high throughput screening, re-engineering the laboratory, and increasing productivity.For more
Projects that require analytical support can evolve from a number of different situations, for example new molecular entities from drug discovery; process changes; packaging changes; site changes; line extensions; and inlicensed projects and compounds. Laboratory automation has been shown to provide a viable and practical solution to assisting in analytical development. However, it is not always the most logical answer. A truly flexible and responsive analytical unit will make a decision on a case-by-case basis, when faced with a new project, whether it is best to: automate some or all aspects/testing involved; contract out to a reputable and approved contract research organization (CRO); hire temporary help; use available in-house resources; use a combination of the options shown above (for example to evaluate the complexity of the new project versus what the in-house resources are currently working on). The paper discusses the advantages and disadvantages of the various options with respect to providing analytical support and suggests optionsfor the most effective use of resources. The role of automation as one of the important tools in the arsenal of these options is highlighted.
High throughput screening (HTS) involves using automated equipment to test a large number of samples against a defined molecular target to identify a reasonable number of active molecules in a timely fashion. Major factors which can influence priorities for the limited resources of the HTS group are projects, productivity, progress and people. The challenge to the HTS group is to provide excellent and timely screening services, but still devote efforts to new technologies and personnel development. This article explains why these factors are so important.
In 1996 and 1997, Glaxo Wellcome's US Research division planned and established their second generation research strategy. An important aspect of the strategy entailed development of two automated screening sites in Biochemistry in Research Triangle Park, NC. Development of the new operations required many decisions to be made very quickly, including automated process design, system selection and site preparation. Descriptions of the decision made in the development of one of the screening sites are presented in this paper.
A pilot study was performed to evaluate the feasibility of using the Internet to securely deliver patient laboratory results, and the system has subsequently gone into routine use in Poland. The system went from design to pilot and then to live implementation within a four-month period, resulting in the LIS-Interlink software product. Test results are retrieved at regular intervals from the BioLink(TM) LIS (Laboratory Information System), encrypted and transferred to a secure area on the Web server. The primary health-care centres dial into the Internet using a local-cell service provided by Polish Telecom (TP), obtain a TCP/IP address using the TP DHCP server, and perform HTTP 'get' and 'post' operations to obtain the files by secure handshaking. The data are then automatically inserted into a local SQL database (with optional printing of incoming reports)for cumulative reporting and searching functions. The local database is fully multi-user and can be accessed from different clinics within the centres by a variety of networking protocols.
The intensifying pressure on reducing the development time for new pharmaceutical products is resulting in an increasing need for laboratory automation. A key element for the successful implementation of robotics for drug product analysis is the establishment of a reliable process for interaction of the automation team with its various customers, for example development product team and manufacturing group. The reduction of cycle time for product development appears to be resulting in more stability studies to support NDA/MAA filings for several reasons. Key clinical information may not be available before initiation of the stability studies and simultaneous world-wide development may result in an increase in the number of product strength and pack options.
There are a number of factors (planning, process optimization, organizational structure, people development and the need to see the total picture) that must be in place for automation to be as effective as possible. This paper discusses these factors and their relationship with automation. It evaluates less obvious areas associated with automation, as well as the more established ones, and discusses the premise that it is the integration of all these aspects that truly offers the biggest opportunities.
Ion mobility spectrometers (IMS) are small, lightweight, extremely robust devices with low power requirements, no moving parts, no absolute requirement for gases or vacuums, that can be operated at ambient temperatures and pressures, and yet are capable of measuring vapour phase concentrations of organic chemicals at very low levels (sub-mug/l). IMS are capable of analysing complex mixtures and producing a simple spectral output. Volatile components produce measurable negative and positive product ions in the spectrometer through chemical ionization. The spectra produced are essentially the vapour phase fingerprints of the target molecules/mixture. Quantitative data can be obtained provided instrument response is within the linear dynamic range of these instruments, but most practical applications of IMS have used the technology in a qualitative manner in situations which require just an above/below threshold or positive/ negative response.In the manufacturing industry there are many examples where the aroma/odour of raw materials has safety or product quality implications. IMS was not developed to replace traditional methods of analysis, e.g. GC/MS or sensory panels, but rather to provide a rapid, qualitative response complementary to more established methods. This paper reports on the use of a hand-held ion mobility spectrometer to characterize the vapours produced by volatile organic compounds,fresh herbs and retail spice mixtures at ambient temperature and pressure. The results show that by monitoring in both ion acquisition modes, ion mobility spectrometers are capable of discriminating between a wide range of products.
C-reactive protein (CRP) levels were measured using a new particle-mediated immunoassay. Tests for precision and linearity of this method gave satisfactory results. The minimum sensitivity of the assay was 1 ng/ml. Interference by bilirubin (<220mg/l) and haemoglobin (<20g/l) was not observed. Using this method, CRP was assayed as a means of monitoring for infection in newborns up to 72 h after delivery. The pattern of time course elevation curves was similar for both groups (10 healthy subjects and 26 patients), but the serum CRP (ng/ml) of infected newborns rose significantly higher than in healthy subjects at 24 h after birth. The rate of increase of CRP (CRP; ng/ml/h) may be a more useful parameter to detect infection, since a significant change in CRP was apparent only 12 h after birth. The reported method was reliable and the parameters obtained were considered clinically useful for early detection of infection.
This paper describes rapid, simple microwave-assisted leaching/ digestion procedures for total and mercury species determination in sediment samples and biomaterials. An open focused microwave system allowed the sample preparation time to be dramatically reduced to only 24 min when a power of 40-80 W was applied. Quantitative leaching of methylmercury from sediments by HNO(3) solution and complete dissolution of biomaterials by an alkaline solution, such as 25% TMAH solution, were obtained. Methylmercury compounds were kept intact without decomposition or losses by evaporation. Quantitative recoveries of total mercury were achieved with a two-step microwave attack using a combination of HNO(3) and H(2)0(2) solutions as extractant. The whole pretreatment procedure only takes 15 min, which can be further shortened by an automated robust operation with an open focused system. These analytical procedures were validated by the analysis of environmental certified reference materials. The results confirm that the open focused microwave technique is a promising tool for solid sample preparation in analytical and environmental chemistry.
The interfacing of a commonly used spectrophotometer, the Hitachi U2000, through its RS-232C port to a IBM compatible computer is described. The hardware for data acquisation was designed by suitably modifying readily available materials, and the software was written using the C programming language. The various steps involved in these procedures are elucidated in detail. The efficacy of the procedure was tested experimentally by running the visible spectrum of a cyanine dye. The spectrum was plotted through a printer hooked to the computer. The spectrum was also plotted by transforming the abscissa to the wavenumber scale. This was carried out by using another module written in C. The efficiency of the whole set-up has been calculated using standard procedures.
A computational program which compares the effciencies of different experimental designs with those of maximum precision (D-optimized designs) is described. The program produces confidence interval plots for a calibration curve and provides information about the number of standard solutions, concentration levels and suitable concentration ranges to achieve an optimum calibration. Some examples of the application of this novel computational program are given, using both simulated and real data.
An automated Cobas Fara method was developed determining the activity of recombinant M. thermophila laccase (rMtL). The chromogenic substrate used was syringaldazine. Under aerobic conditions, rMtL catalyses the oxidation of syringaldazine forming tetrametoxy-azo bis methylene quinone. The developed violet colour was measured kinetically at 530 nm as an expression of the enzyme activity, rMtL is a very sensitive oxidoreductase, therefore many factors had to be carefully controlled in order to get a robust analytical assay. In order to stabilize rMtL, PEG 6000 was added to the enzyme dilution medium. Furthermore, Triton X-I00 was included in the enzyme incubation solution.The analytical as well as technical conditions have been optimized, resulting in a method with good precision, sensitivity and speed of analysis. The Michaelis-Menten constant, K(m), was determined to be 22muM syringaldazine. LOQ was determined to be 0.010 Uml(-1), LOD to be 0.0002 Uml(-1) The analytical range of the enzyme dilution curve was from 0.01 to 0.044 Uml(-1) The repeatability was 1.9%, the reproducibility 3.1%. Testing the robustness of the method showed that the most sensible factors in the rMtL analysis in decreasing range were: incubation temperature, concentration of Triton X-I00, molarity and pH of the incubation buffer, and finally the concentration of syringaldazine.
A monochannel plasma emission spectrometer was converted to a multichannel instrument by the introduction of a detection system based on an array of 1024 photodiodes and a low-resolution dispersion device. The new, relatively inexpensive equipment, features both the high speed typical of simultaneous instruments and the versatility of scanning systems. This paper reports on an evaluation of the modified equipment for quantitative analysis with the simultaneous determination of Al, Mn, Mg, Ca, Fe and Cu in a natural water matrix. An average relative prediction error of 2.4% was found which is the same as the error obtained with the conventional analytical method. Data acquisition with the modified instrument is up to 40 times faster.
