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In highway construction, completing projects on time is critical. However, when projects are not completed on time, one of the aspects that is often neglected by the state departments of transportation (DOTs), which causes delays in highway construction, is project closeout. The project closeout phase, if delayed, not only has consequences for transportation agencies and contractors, but also leads to substantial social costs to the public. Despite the potential magnitude of the impact, there is limited knowledge about the factors that cause project closeout delays or about strategies for timely highway construction project closeouts. This study identified the causes that delay highway project closeouts, raises awareness of the implications of delays, and provides recommendations for efficient highway project closeout practices. The research methodology included an extensive literature review, a survey questionnaire (40 state DOTs participating), and case studies of eight state DOTs. The results showed that difficulties in attaining the required documentation, claims and litigations, managing multiple funding sources, a lack of urgency from local utilities/entities, and the lack of sufficient DOT project staff are major factors that delay project closeout. When a highway construction project is not closed out in a timely manner, the DOT can be subject to additional costs, obsolete funding sources, loss of project documentation, loss of staff with project knowledge (through retirement/attrition), and potential adverse impacts on internal and external relationships. The authors provide recommendations for state DOTs to mitigate closeout delays and help ensure timely finalization of highway construction projects.

1. Plasma and whole blood concentrations of proguanil and its two major metabolites cycloguanil (CG) and 4-chlorophenylbiguanide (CPB) were measured by a sensitive h.p.l.c. technique in nine healthy adult male volunteers after a single oral dose of proguanil 200 mg. 2. Proguanil was absorbed with a median time to peak plasma concentration of 3 h (range 2-4 h). 3. Peak plasma concentrations of proguanil ranged between 150 and 220 (median 170) ng ml-1 compared with 12 to 69 (median 41) ng ml-1 for the active antimalarial metabolite CG, and 3 to 16 (median 11) ng ml-1 for CPB. Peak (mean +/- s.d.) plasma CG concentrations occurred 5.3 +/- 0.9 h and peak CPB concentrations occurred 6.3 +/- 1.4 h after oral administration of proguanil. 4. Whole blood concentrations of proguanil were approximately five times higher, and whole blood CPB concentrations were four times higher than corresponding plasma values, whereas plasma and whole blood concentrations of CG were similar. 5. A triexponential function was fitted to these data; mean (+/- s.d.) values for the AUC were 3046 +/- 313 ng ml-1 h for proguanil, 679 +/- 372 ng ml-1 h for CG and 257 +/- 155 ng ml-1 h for CPB. 6. Plasma and whole blood concentrations of proguanil and its metabolites declined in parallel with terminal elimination half-lives estimated as 16.1 +/- 2.9 h and 15.7 +/- 2.4 h, respectively. Mean residence times in plasma and whole blood were estimated as 21.2 +/- 4.9 and 19.3 +/- 2.4 h.

Slices cut from skeletons of massive Porites display two types of luminescence when illuminated by ultra-violet (UV) light: (1) faint luminescent banding associated with the annual skeletal density banding pattern and (2) narrow lines of strong luminescence associated with monsoonal runoff of fresh water from nearby land. Barnes and Taylor [Barnes, D.J. Taylor, R.B. 2001a. On the nature and causes of luminescent lines and bands in coral skeletons. Coral Reefs 19, 221–230] showed how larger skeletal holes could give rise to increased luminescence—thus accounting for the link between skeletal density banding and faint luminescent banding. Work described here tests the notion that strongly luminescent lines are also regions of lower skeletal density. Experiments involving real and artificial coral skeletons indicated that likely changes in hole size in real skeletons cannot account for the amount of luminescence associated with luminescent lines. Larger particles (

Summary Background The quality of medicines available in some less-developed countries is inadequate in terms of content of active ingredient. Reasons for the poor quality of drugs include widespread counterfeiting of medicines in less-developed countries, excessive decomposition of active ingredient as a result of high temperature and humidity, and poor quality assurance during the manufacture of medicinal products. Our aim was to investigate the quality of different drugs obtained from retail pharmacies in two urban areas of Nigeria, and, in instances of poor quality, to ascertain the reason why. Methods We randomly collected 581 samples of 27 different drugs from 35 pharmacies in Lagos and Abuja in Nigeria. We analysed the medicines for drug content by validated chromatographic methods, and compared our results with pharmacopoeial requirements. Findings 279 (48%) samples did not comply with set pharmacopoeial limits, and this proportion was uniform for the various types of drugs tested. Although some preparations contained no active ingredient, most had amounts just outside the pharmacopoeial limits. We identified samples with both too much and too little active drug content. Interpretation The most probable cause of the poor quality of drugs is absence of adequate quality assurance during manufacture. Substandard drugs sold in the pharmacies of less-developed countries could contribute to global microbial resistance and therapeutic failure of infectious diseases.

The method of applying large sample volumes in micellar electrokinetic chromatography termed sweeping is applied to determine the conservative limits of detection of some basic drugs in plasma and urine. The biguanides proguanil, 4-chlorophenylbiguanide and cycloguanil are used as models of basic drugs and the limits of detection obtained compared with those previously reported for capillary zone electrophoresis using field-amplified sample injection (FASI) and also by LC using off-line preconcentration. It is found that the sweeping method can be applied to extracts of such biological matrices. The limits of detection obtained by sweeping are improved over FASI for plasma but not for urine and the limits of detection are higher than those reported for LC, for these compounds.

A reversed-phase HPLC method previously developed for the analysis of progesterone and its major metabolites has been transferred successfully to a capillary electrochromatography (CEC) system. Procedures for fabricating packed capillaries and the modifications made to the capillary electropherograph which allow operation in the CEC mode without pressurisation are described. The dependence of electroosmotic flow on electric field strength, pH and organic modifier content is discussed. Direct comparison with HPLC shows that CEC provides useful gains in efficiency and speed of analysis and requires vastly reduced amounts of both chromatographic phases and material for analysis. On-line concentration is described which allows the lower sensitivity of CEC to be offset by injecting analytes from a non-eluting solution. Examination of steroids in plasma demonstrates that the superior separation by CEC is maintained in a complex biological matrix.

In a number of developing countries there is reportedly a high incidence of the availability of substandard drugs. The majority of these reports do not contain quantitative data to support these claims, nor do they describe the methodology employed for the quality assessment. Many assume counterfeiting as the reason for the poor quality and in some cases this is not justified. We collected 96 samples of chloroquine and selected antibacterials from Nigeria and Thailand in a controlled and methodical manner and analysed them using appropriately validated methods based on high-performance liquid chromatography capable of detecting drug-related impurities and quantifying active drug(s). The results indicate that 36.5% of the samples were substandard with respect to pharmacopoeial limits. Decomposition was the cause of poor quality in a number of the samples but overall, poor manufacturing appeared to be prevalent. The analyses generated little evidence to indicate fraudulent manufacturing. Treatment failure and drug-resistance are possible consequences of the use of substandard drugs.

The retention behaviour of the quaternary ammonium compounds benzalkonium chloride, cetylpyridinium chloride and dequalinium chloride on a 100 × 4.6 mm id cyanopropyl stationary phase column is reported as a function of organic modifier and ionic hydrophobic mobile phase additive concentrations. Optimum liquid chromatographic mobile phases using different mobile phase additives are reported which are suitable for the determination of cetylpyridinium chloride and dequalinium chloride in a variety of candy-based lozenge formulations. The quantitative aspects of assays based on the separation of active ingredients and formulation excipients were established. The generality of application of the assay methods was evaluated by determining the quaternary ammonium content of different lozenges and comparing the values obtained with the stated dose

A method for the separation of a mixture of opiates comprising pholcodine, 6-monoacetylmorphine, morphine, heroin, codeine and dihydrocodeine by capillary electrophoresis using a running buffer of 100 mM disodium hydrogenphosphate at pH 6 is described. The characteristics of an analytical method based on this separation for the determination of these drugs following extraction from urine and using levallorphan as internal standard are reported. Detection limits in the region of 10 ng cm −3 are achieved when using electrokinetic injection. A comparison is made of the sensitivity and reproducibility of electrokinetic and hydrodynamic injection for these drugs. Data are presented to show the results obtained when the proposed method is applied to urine spiked with all the above opiates and also to urine from a subject following consumption of dihydrocodeine and pholcodine. The concentrations found are compared with those obtained by LC.

Numerical models of skeletal growth in Porites (Taylor et al., 1993,1995) are extended to examine the likely distribution of trace materials which become included in skeleton as the result of a continuous, annual cycle in their environmental concentration or in their uptake from the environment. Modelling suggests that the amplitude, profile and apparent timing of variations in the concentration of trace materials along skeletal growth axes may differ greatly from the amplitude, profile and timing of causative variations in the environment. Alterations of the recorded signal are associated with coral growth parameters such as annual extension rate and the depth of skeleton occupied by tissue, and with annual cycles in the density at which skeleton is deposited and annual cycles in skeletal extension rate. The models also indicate that the annual average obtained for the signal recorded in coral skeletons will vary from the annual average of the causative, environmental signal. Examples of recording of continuous, annual, environmental cycles by corals are temperature-related variations in skeletal concentration of 18O and strontium. Published information about these coral thermometers is examined in terms of output from the models. The models are used to examine errors that may result from overly simplistic interpretation of temperature information stored in coral skeletons.

Trace materials included in coral skeletons during growth provide three distinct types of proxy environmental record; long-term (years to decades), annual and short-term or “pulse” records. Long-term records are not likely to be affected by skeletal growth mechanisms because these mechanisms operate at annual or shorter time scales. However, annual and pulse records will be affected by annual cycles in skeletal density and extension rate, and by mechanisms which control the time and position in which new skeleton is added. Numerical models of skeletal growth in Porites (Taylor et al., 1993) are extended and used to examine the effect of growth mechanisms upon pulse inclusions. The results suggest that useful proxy records can be recovered by optical measurements of lines which can be seen, or which can be made visible, in a section sawn along a skeletal growth axis. The results suggest that it will be difficult to recover records of pulse events from measurements of the concentration of trace material in the skeleton. Overall, the results reinforce recent suggestions that understanding of coral skeletal growth mechanisms is fundamental to recovery of reliable proxy environmental records from massive corals.

Cows that were subjected to hot environmental temperatures yielded less milk (3.1 kg/d) on a diet high in CP (18.4%) and of medium degradability (65%) than on diets high in CP of low degradability (59%) or medium in CP (16.1%). The high CP diets were associated with decreased DMI and higher water intake, ruminal NH4, and blood urea. Negative effects on yield from the high CP, medium degradability diet were not observed at moderate temperatures. Evaporative cooling of cows in hot weather resulted in a greater milk yield response to low versus medium rumen-undegradabale protein diets than for uncooled cows. Evaporative cooling of cows also affected response to protein quality. For cooled cows, high Lys diet (soybean, fish, and blood meals) increased milk yield 14% over that with low Lys diet (corn gluten meal), but, for uncooled cows, a high Lys diet only increased yield by 9%. Percentage of CP, degradability, and protein quality had no effect on body temperatures or respiration rates of lactating cows. Some, but not other, reports showed that supplementation of 2 to 2.5% fat to diets fed under hot summer conditions resulted in less yield response than when fat was added at moderate temperatures. In several studies, fungal cultures (3 to 5 g/d) in the diet decreased body temperatures and respiration rates in hot, but not cool, weather. Increased milk yields and cellulose digestibility also resulted from dietary fungal cultures in some, but not all, trials. The mechanism of action exerted by fungal cultures on body temperature and respiration rate is unclear.

Chromatographic separations of the components of polymyxin B sulphate are reported and it is shown that the separations are such that two of the three major components detected are specific for the intact drug in the presence of chemical decomposition products. The specificity of the separations with respect to other antibacterials, propamidine, dibromopropamidine and trimethoprim is also reported. Validation of the stability indicating assay based on this separation is described. Rate constants for the decomposition of polymyxin at various temperatures between 32 and 52°C and in solutions of different pH values from 2.0 to 10.3 are determined and the t 90 value at pH 7 and 4°C is estimated.

X-radiographs of slices cut from massive skeletons of Porites appeared to show more corallites than are present on the slices. The ratio of apparent:real corallites averaged 1.21 ± 0.09 in slices cut from 25 colonies of Porites . This phenomenon was tested by computer-simulated X-radiography of a “slice of skeleton” made up of perfectly packed hexagons. The hexagons simulated corallites. The “slice” was “X-radiographed” at different angles and resulting “density” profiles were averaged. The main contribution to the average profile came from zigzag arrangements of walls within the hexagonal pattern. This arrangement combined with occasional end-to-end arrangements of walls to give a frequency of density peaks slightly higher than the frequency of hexagons. This model is presented as a plausible explanation for the number of corallites apparently seen in X-radiographs.

The influence of pH, ionic strength and buffer concentration on the stability of josamycin has been investigated. The pH-rate profile for josamycin over the pH range 1–12 was characterised and the equation describing the profile determined. Results indicated that josamycin is subject to specific acid catalysis whilst catalysis in alkali media appeared to be more complex. The rate constant for catalysis by hydronium ion ( k H ) was 54.11 M −1 · h −1 and the rate constant for catalysis by hydroxide ion ( k OH ) was 60.35 M −1 · h −1 . Catalysis due to water was insignificant and the water catalysed rate constant was found to be 3.37 × 10 −5 h −1 . The pH of maximum stability was determined as pH 6.5 whilst degradation at pH 1.0 and 12.0 is about five orders of magnitude greater than at pH 6.5. The degradation of josamycin in acid is subject to a significant primary salt effect; however, no secondary salt effect was evident. Concentration vs. time profiles for josamycin in acidic media were biphasic which indicated that the degradation reaction did not follow a simple pathway whereby josamycin degrades directly to products. Further investigations suggest that josamycin undergoes a reversible isomerisation step, with subsequent degradation of josamycin and possibly its isomer, by cleavage of the mycarose moiety to desmycarose compounds. Studies to determine the stability of josamycin in simulated gastric fluids demonstrated that acid degradation could be appreciable after oral administration. However, extensive degradation in vivo will only occur at the most acidic gastric pH's of about pH 1.0 to 2.0.

Bacterial uptake determinations were performed to evaluate the antibacterial effects of trimethoprim, sodium sulphadiazine and dibromopropamidine isethionate against Enterococcus faecalis together with checkerboard assays and agar diffusion determinations. The reciprocal effects of trimethoprim (17.5 μg/) and sodium sulphadiazine (100 μg/ml) against E. faecalis culture produced cell uptakes of 14-times the concentration of sodium sulphadiazine and 5-times the concentration of trimethoprim. Folinic acid partially reversed the bacterial uptakes.

Three growth processes in massive colonies of Porites are incorporated into simple, mathematical models of skeletal density band formation. The growth processes are (i) extension of the colonial skeleton at its outer surface, (ii) thickening of skeleton through the depth of skeleton occupied by tissue and (iii) periodic, essentially monthly, uplift of the lower margin of the tissue layer. As far as possible the models are constructed using realistic values for parameters associated with growth. The growth processes are driven or modulated by a single, sine wave, forcing function which could correspond to annual changes in environmental parameters such as light and temperature. Extension and thickening are allowed to vary with the forcing function or are held constant. This generates four models. All models display a pattern of fine, monthly density bands associated with periodic uplift of the lower margin of the tissue layer. The models with variable thickening show that density bands can appear to be formed several months out of phase with the forcing function. Both appearance and apparent timing of density bands vary in models with variable extension and variable thickening. These are also affected by the ratio of the depth of skeleton occupied by tissue to annual extension and by intra-annual (seasonal) change in extension. These simple, realistic models may reconcile many of the apparent contradictions which surround coral density banding.

Modifications of antibacterial activity have been demonstrated using combinations of two antibacterials from trimethoprim, sulfonamides (sulfadiazine, sulfamerazine, and silver sulfadiazine), silver nitrate, and dibromopropamidine isethionate, either formulated in a cream base or dissolved in peptone water. The creams were evaluated using the agar cup diffusion method in isosensitest agar. The peptone water solutions provided fractional inhibitory concentrations for combinations of the antibacterial substances. The test organisms were Pseudomonas aeruginosa, Enterobacter cloacae, and Staphylococcus aureus. Bacterial uptakes of antibacterial combinations, determined by either an HPLC assay method or an atomic absorption method, combined with dry cell weight determinations, indicated that enhancement of activity of the antibacterial combinations against P. aeruginosa (two strains) and E. cloacae were related to marked increases in the bacterial uptake of the chemical agents. Decreases in activity were related to decreased uptake of either dibromopropamidine and/or silver ions. The effect of the trimethoprim and the sulfonamides was shown to depend on their effect on bacterial folate synthesis. It is suggested that partial blockade of the folate synthetic pathway leads to an effect on cell permeability which results in increased uptake of antibacterials. Dibromopropamidine isethionate also has an effect on cell permeability which produces an increased bacterial uptake of a second antibacterial present in the medium. These findings provide further explanation of how subinhibitory concentrations of trimethoprim and sulfonamide combinations are synergistic against a wide range of bacteria even when certain bacteria are resistant to either member of the combination.

A reversed-phase isocratic high-performance liquid chromatographic method for the determination of total teicoplanin in plasma is reported. The method developed uses a bracketing injection technique in conjunction with large injection volumes on a 1 mm diameter column to form a limited injection-generated gradient. The chromatography yields adequate resolution among all the major components for individual quantitation and also allows quantitation of total teicoplanin in plasma using ultraviolet detection. Pretreatment is by solid-phase extraction which uses C8 Bond Elut cartridges and gives effective clean up from endogenous materials. The method offers a faster and simplified means to determine total teicoplanin in plasma than those previously reported, and has a detection limit of 50 ng/ml.

Two trials compared four treatments in a randomized block design with a 2 × 2 factorial arrangement of treatments using lactating Holstein cows. Factors were two concentrations of protein degradability (high, 61 to 64%; low, 47 to 55% degradable intake protein) and two types of environment (shading versus shading plus evaporative cooling). In trial 1 (24 cows for 55 d), evaporative cooling resulted in increases in production of milk, 3.5% FCM, gross efficiency of conversion of feed to milk, and DM intakes. The diet of greater protein degradability also increased milk production. There were no significant differences in milk composition. In trial 2 (36 cows for 50 d), cows fed less degradable protein produced more milk of higher lactose and lower fat and protein contents. Protein degradability by evaporative cooling interactions were significant for milk production and efficiency of conversion of feed to milk, with the low degradable protein diet resulting in higher milk yields and efficiencies in cooled than in shaded cows. During both trials, cooling decreased respiration rates and rectal temperatures, but protein degradability had no effect. The different production response between trials probably was due to hotter conditions and a higher quality of rumen undegradable protein in trial 2 than in trial 1. Trial 2 data suggest that feeding of low degradable protein improves milk production during heat stress, provided the undegradable protein is of good quality.

A stability-indicating assay method is described for proguanil based on reversed-phase ion-pairing HPLC. Using this method a study of the stability of proguanil in solution is made. In solution, proguanil decomposes by a first-order reaction. It is shown that the major decomposition product is 4-chloroaniline and that two other minor products can be detected but not identified. First-order rate constants over the temperature range 40–90°C are determined and an activation energy of 90.8 kJ mol −1 derived. The log k -pH profile is determined and indicates maximum stability in the range pH 6–8. From the magnitudes of the rate constants obtained, it is evident that proguanil is a very stable drug in solution. The effect of ultraviolet radiation on proguanil is to produce the same decomposition products. The effects of thermal stress and ultraviolet on a tablet formulation of proguanil (Paludrine ∗ ) are also studied and these further confirm the stability of this compound to both thermal and photochemical stress.

We describe a novel, integrated organic-inorganic waveguide/photodetector with an internal quantum efficiency of (53/spl plusmn/15%). Low-loss (2.7/spl plusmn/0.3 dB/cm at /spl lambda/=1.064 /spl mu/m for 10-/spl mu/m wide waveguides) crystalline organic waveguides are grown directly onto the pre-processed InGaAs photodetector by organic molecular beam deposition (OMBD) without affecting either the dark current or capacitance of the photodiode. The polarization-preserving nature of the waveguides suggests that a patterned substrate significantly influences the organic molecular orientation during vacuum deposition.

The evolution of the Bras d’Or Lakes since the retreat of the last ice sheets c. 15 ka (thousands of radiocarbon years before present, where present is defined as 1950) is inferred from multibeam bathymetry, seismic reflection profiles, and sediment cores. The thickness of stratified sediment in the Lakes overlying glacial till shows that there was a step-like retreat of ice towards a late ice centre in the western part of the Bras d’Or Lakes. As ice retreated, a lake formed in the area of the modern Bras d’Or Lakes and probably drained through Little Bras d’Or Channel. Ice retreat and sea level change on the continental shelf off south-eastern Cape Breton are inferred from multibeam bathymetry that shows proglacial subaerial river channels and suggests that sea level was perhaps 50 m lower than present about 15 ka. Relative sea level appears to have risen subsequently, so that marine conditions existed in Bras d’Or Lakes basin at 10 to 9 ka. Sea level may have risen to -15 m (below modern sea level)before falling again in the early Holocene. This falling early Holocene relative sea level resulted in the creation of freshwater lakes, with a prominent erosion surface at -25 m marking the lake level in some areas. Rising sea level then resulted in a return to marine conditions in the Lakes by 4 to 5 ka. L’évolution des lacs Bras d’Or depuis le retrait des dernières nappes glaciaires il y a 15 000 ans se révèle par la bathymétrie multifaisceaux, les profils de réflexion sismique et les carottes de sédiments. L’épaisseur des sédiments stratifiés dans le till sus-jacent des lacs démontre qu’il y a eu un retrait en escaliers des glaces vers un centre fini-glaciaire situé dans la partie occidentale des lacs Bras d’Or. Les eaux, libérées lors du retrait des glaces, s’échappèrent probablement via le canal du Little Bras d’Or pour former un lac dans le lit actuel des lacs Bras d’Or. Le retrait des glaces et les changements du niveau de la mer sur la plateforme continentale au sud-est de Cap-Breton sont mis en évidence par la bathymétrie multifaisceaux, qui montre des lits de rivière sub-aériens proglaciaires et indiqueque le niveau de la mer se trouvait peut-être à 50 m plus bas qu’aujourd’hui il y a environ 15 milles d’années. La hausse du niveau de la mer depuis cette époque a provoqué l’inondation des lacs Bras d’Or ancestraux il y a de 9 à 10 milles d’années, et le niveau des eaux aurait atteint -15 m avant de chuter au début de l’Holocène. Cette chute relative du début de l’Holocène a résulté en la création de lacs pour une seconde fois, avec une importante surface d’érosion à -25 m qui marque le niveau des eaux dans certaines zones. Ces lacs ont été finalement inondés par la mer il y a de 4 à 5 milles d’années.

A chromatographic method is described for the determination of sodium artesunate in plasma. This includes cetyltrimethylammonium bromide as a cationic pairing ion in a reversed-phase system using an octadecylsilica 100×4.6 mm I.D. 3 μm analytical column with a mobile phase of acetonitrile/acetate buffer at pH7. Column switching incorporating a 5 μm octadecylsilica 100×4.6 mm I.D. precolumn is used in addition to off-line solid-phase extraction for pretreatment of plasma samples in order to eliminate interference from endogenous components. Detection is by post-column derivatisation with 1.0 M methanolic KOH followed by UV detection at 289 nm. Calibration is linear over the range 100–1600 ng ml −1 and the limit of detection is estimated as 20 ng ml −1 . Illustrative results are shown of the artesunate plasma levels determined by the proposed method following the administration of artesunate as tablets and as suppositories to healthy volunteers.

The pharmacokinetics of orally administered proguanil and its metabolites were determined in six healthy volunteers and in six peptic ulcer patients, before and after a 3-day course of cimetidine (400 mg given two times daily for 2 days and 400 mg on the third day 1 h before proguanil). Cimetidine significantly increased Cmax (P0.05), AUCo-alpha (P0.005) and elimination half-life t 1/2b of proquanil in plasma of healthy subjects. In ulcer patients, cimetidine significantly increased, AUCo-alpha (P0.05), elimination half life (P0.005) and Cmax. Cimetidine significantly reduced (P0.05) Total body clearance in both healthy subjects and in peptic ulcer patients. The Cmax and AUCo-alpha of the active metabolite cycloguanil was significantly decreased (P0.05) in both the healthy subjects and in the peptic ulcer patients. The Cmax of the inactive metabolite, 4-CPB was significantly decreased in healthy subjects and AUCo-alpha significantly decreased in peptic ulcer patients.

A literature survey on published reports of the determination of drugs in biological fluids shows that all methods of sample pretreatment have been used and that the limits of detection achieved vary widely, ranging from low ngcm(-3) to microgcm(-3). The most widely used injection method was hydrodynamic and, in the majority of cases, whenever low detection limits were achieved, this was a result of preconcentration during the sample pretreatment. Only a small proportion of the reported methods employed electrokinetic injection and utilised the field amplified sample injection (FASI) techniques. An experimental investigation of the alternative hydrodynamic and electrokinetic injection methods for a small set of antimalarial drugs is reported. It was found that electrokinetic injection with FASI from an acetonitrile-water matrix produced dramatic improvements in detection limits. This improvement could not, however, be achieved when the drugs were in plasma using protein precipitation, liquid-liquid extraction or solid phase extraction pretreatment methods. This highlights the importance of sample pretreatment in utilising the potential sensitivity of capillary electrophoresis with electrokinetic injection.

A method for the specific determination of three quaternary ammonium compounds, benzalkonium chloride, cetylpyridinium chloride and dequalinium chloride, used as antibacterial agents in candy-based lozenges, is described based on capillary zone electrophoresis. It is shown that, following optimisation of buffer composition with respect to organic modifier concentration, pH and buffer concentration together with the inclusion of sodium dodecylsulphate as an ion-pairing agent in the case of dequalinium chloride, these analytes migrate in less than 5 min. The resultant electrophoretic peaks are sharp and readily quantified. The individual alkyl components of benzalkonium chloride can be resolved as can related impurities in dequalinium chloride lozenges. The quantitative characteristics of the assay method, based on peak areas normalised with respect to migration times, are reported and the method is compared with a previously published method based on liquid chromatography.

A separation of heroin, 6-monoacetylmorphine, codeine, pholcodine, dihydrocodeine and morphine using a 200 x 2 mm I.D., 3 microns silica column with dichloromethane-pentane-diethylamine-methanol mobile phase is described. Data on the determination of these compounds in a urine matrix based on this separation using a solid-phase pretreatment with Bond Elut Certify cartridges and nalorphine as an internal standard are shown. The compounds listed can be quantified at levels below that generally accepted as the cut-off level for the screening for opiates by enzyme immunoassay (EMIT) with detection limits for the different opiates ranging from 4 to 20 ng ml-1. Comparative data are shown of subject urine samples assayed for opiates by both the enzyme immunoassay and the proposed method. The utility of the method for the elimination of so-called false positives detected by EMIT due to the presence of medically prescribed and non-prescription opiates in urine is discussed.

Interest in crystalline organic semiconductors has increased recently due to their diverse optical and electronic properties which have numerous device applications. Considerable effort has been focused on utilizing the large optical nonlinearities found in many of these materials.1 One crystalline organic semiconductor: 3,4,9,10 perylenetetracarboxylic dianhydride (PTCDA), has been of particular interest due to its excellent electronic properties, giant dielectric anisotropies2 and potential uses in optoelectronic devices. Recent research with PTCDA has yielded considerable success with waveguide structures.3,4 Special properties of PTCDA such as low optical absorption loss at near-infrared wavelengths, environmental stability, and capability of patterning make waveguide integrated devices and organic - semiconductor hybrid devices very attractive.

The separations of 11 antimalarial drugs and metabolites are shown by CZE at low pH and by MEKC at high pH. CZE is shown to be superior to MEKC in resolution capability for these compounds under the conditions examined. Both are shown to provide different selectivities to those obtained by ion-pair reversed-phase HPLC. The effect of sample injection solvent is examined in CZE and it is shown that field-amplified sample injection is effective for these compounds. In addition, it is shown that injection of sample in an organic solvent such as methanol augments the stacking of analytes resulting in lower detection limits. The limit of detection of some antimalarials in a urine matrix is reported.

Plasma and whole blood concentrations of proguanil, its active metabolite cycloguanil, and the inactive metabolite 4-chlorophenyl-biguanide, were measured by HPLC in 10 healthy Karen women in the last trimester of pregnancy, following a 200 mg single oral dose of proguanil. Four of these women were restudied 2 months after delivery. The pharmacokinetic properties of proguanil were similar during and after pregnancy. Median peak plasma concentrations of proguanil during pregnancy and following delivery were 212 and 215 ng.ml-1, and occurred at 4.5 and 5 h, respectively. Mean plasma AUC values for proguanil during and following pregnancy were 94 and 98 ng.h.ml-1.kg-1, respectively. Corresponding whole blood AUC values were 361 and 396 ng.h.ml-1.kg-1. The mean elimination half lives and mean residence times of proguanil in plasma and whole blood were 12.3 and 19.6 h and 13.8 and 20.7 h respectively during pregnancy. Following pregnancy these values were 17.1 and 19.7 h for plasma and 19.7 h and 20.2 h for whole blood respectively. Mean peak plasma and whole blood concentrations of cycloguanil following pregnancy were 25 and 22 ng.ml-1 respectively. During pregnancy peak cycloguanil concentrations in both plasma and whole blood were markedly lower, 13 and 12 ng ml-1, respectively. Two pregnant women (neither of whom were restudied) were probably poor metabolisers of proguanil. The mean ratio of proguanil to cycloguanil plasma AUC was 16.7 in the third trimester of pregnancy and 7.8 following pregnancy, compared with less than 5 in previously reported studies.(ABSTRACT TRUNCATED AT 250 WORDS)

A general separation strategy, involving solid-phase extraction followed by reversed-phase ion-pairing HPLC with an organic counter ion for a set of 11 widely used antimalarial drugs and metabolites has been developed. The basis underlying the separation has been explored and work, including quantitative data, has been carried out on illustrative separations which form the basis of novel quantitative assays of groups of antimalarials which are relevant to current prophylaxis and treatment of malaria.

A general high-performance liquid chromatographic (HPLC) procedure is described which allows the assay of several antibacterial drugs in combination in a matrix of bacterial cell cultures. The drugs assayed were dibromopropamidine, trimethoprim, sulphadiazine and sulphamerazine. It is also shown that p-aminobenzoic acid, which is an essential metabolite of many micro-organisms, does not interfere and can itself be quantified. The method uses solid-phase extraction on a cyclohexyl-bonded silica with subsequent separation of the analytes by reversed-phase HPLC. Tetrabutylammonium is used in order to reduce the retention of trimethoprim and dibromopropamidine and quantification is by ultraviolet detection at 254 nm. The analytical characteristics of the proposed method are shown for certain drug combinations.