Laboratory Information Management Systems--part I. Concepts.

The purpose of this analytical survey is to give a summary of some of the main design features that can be incorporated into a Laboratory Information Management System (LIMS), in the context of the total automation of the laboratory. Additionally it will give potential purchasers of such systems some essential background knowledge and a summary of our experiences. The survey is presented in two parts: the first covers the features and the possible concepts that could be used in a LIMS system. This is followed in the second part by an outline of the stages of acquisition, validation and benefits of such a system. Together the two articles provide the information required to aid the design and installation of a LIMS. This first section deals with the possible features that a laboratory could include when contemplating the installation of such a system: the basic tools that are required for a LIMS, the database and the computer equipment are discussed. This is followed by the interfacing of analytical instruments and central versus distributed processor philosophy. The various screen formats available and the use of bar codes as a means of identifying samples and for rapid data entry into the computer system are discussed.

Laboratory Information Management Systems--part II. Implementation.

In this, the second of two articles on Laboratory Information Management Systems (LIMS), the stages of the acquisition of a system are discussed. First, the laboratory automation strategy is developed leading to the writing of the requirements specification sent to prospective suppliers. The next step, in conjunction with the chosen supplier, is to write the functional and systems specifications from which the LIMS will be tailored. Once installed the LIMS must be validated and in the event of hardware or software changes, should undergo partial or full re-validation. The education and training of users, and operational considerations are presented before concluding with possible developments of LIMS in the future.

Fully automated assay for the determination of GR117289X in human plasma using mixed mode solid-phase extraction and high-performance liquid chromatography with ultraviolet detection.

GR117289X, 3-(3-Bromo-2-[2-(1H-tetrazol-5-yl)-phenyl]-bezofuran-5-yl methyl)-2-butyl- 5-chloro-3H-imidazole-4-carboxylic acid, 1, is an angiotensin II receptor antagonist. A sensitive, accurate and precise assay for the determination of 1 in human plasma and validation data is described. The assay consists of a novel solid-phase extraction using Certify II followed by a reversed-phase gradient HPLC separation with UV detection. The extraction procedure has been fully automated by a Zymate XP robot and linked on-line to the HPLC system. The analytical range for the assay is 5-250 ng ml-1 over which the assay is linear and specific for 1 with respect to endogenous plasma components and its tetrazole N2 glucuronide, the major circulating metabolite 2. For the fully automated procedure the intra-assay data indicate a maximum bias and coefficient of variation across the calibration range of +8.0 and 9.4%, respectively. The inter-assay data indicate a maximum bias and coefficient of variation across the calibration range of +8.0 and 11.1%, respectively. The extraction efficiency of the assay was approximately 75%. Both a manual and fully automated assay were applied to the analysis of 1 in plasma of volunteers from a number of clinical studies. The assay has been shown to be robust in sustained use over several months.

Liquid-solid sample preparation in drug analysis.

This article compares liquid-solid extraction (LSE) with the more conventional liquid-liquid extraction (LLE) for the preparation of biological samples for assay. The commercially available manual LSE methods, Sep-Pak and Bond Elut, as well as the automated instruments Prep and Analytichem Automated Sample Processor (AASP), are reviewed. Using examples from the literature and the authors' own experiences a practical guide is given to the advantages and disadvantages of LSE.

Sample preparation for the HPLC analysis of drugs in biological fluids.

Sample preparation for the analysis of drugs in biological fluids consists of a number of unit operations that are used for (i) release of the drug from a conjugate or biological matrix; (ii) removal of endogenous compounds that could interfere with the assay; and (iii) techniques for liquid handling. The trends in sample preparation that have occurred over the past 10 years in the authors' laboratory are discussed. In general, there has been a move from the traditional liquid-liquid extraction to methods using bonded-silica which permit rapid throughput and efficient extraction. Automation of sample preparation has seen further gains in productivity; however, the present generation of equipment lack the control and communication systems that are essential for the development of the automated integrated laboratory of the future.

High-performance liquid chromatographic determination of oxmetidine in human plasma: comparison of liquid-liquid and liquid-solid extraction techniques.

A preliminary liquid-solid sample preparation scheme (LSE) for the HPLC determination of oxmetidine in human plasma is compared with the existing liquid-liquid extraction. The LSE method shows great practical advantages, such as ease of preparation, saving of time, and smaller sample volumes, but needs to be investigated further with respect to robustness and the removal of an endogenous compound that interfered with the quantitation of oxmetidine at low concentrations.

Two systems for the automated analysis of drugs in biological fluids using high-performance liquid chromatography.

This paper describes two fully automated assays. One for zaprinast, a cGMP specific phosphodiesterase inhibitor, which uses the Gilson-Advanced Automated Sample Processor combination, and the other for an H+/K+ ATPase inhibitor and its sulphone metabolite, which uses direct injection. Both assays were developed to support pharmacokinetic studies at therapeutic doses in small animals as well as in man. Plasma or serum (20-200 microliters) is placed directly into an autosampler and all subsequent manipulations are performed mechanically.

Intracellular inhibition of human neutrophil elastase by orally active pyrrolidine-trans-lactams.

Described are the acylation binding of trans-lactam 1 to porcine pancreatic elastase, the selection of the SO2Me activating group for the lactam N which also confers metabolic stability in hamster liver microsomes, the introduction of aqueous solubility through the piperidine salt 9, the in vivo oral activity of 9 and its bioavailability, and the introduction of 9 as an intracellular neutrophil elastase inhibitor.

The discovery of a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase--GW311616A a development candidate.

The discovery of a potent intracellular inhibitor of human neutrophil elastase which is orally active and has a long duration of action is described. The pharmacodynamic and pharmacokinetic properties of a trans-lactam development candidate, GW311616A, are described.