[Hyperammonemia originated from the test tube not from the patient].
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Ammonia↗
Biomedical subjects
Y Bergqvist
Publications and source records attributed to Y Bergqvist.
Determination of mefloquine in blood, filter paper-absorbed blood and urine by 9-fluorenylmethyl chloroformate derivatization followed by liquid chromatography with fluorescence detection.
We describe a method for determination of mefloquine (MQ) in 100-microliters samples of urine, whole blood, and capillary blood collected on filter paper; quantification is by liquid chromatography with fluorescence detection at 475 nm of the 9-fluorenylmethyleneoxycarbonyl derivative. Whole blood and urine samples were prepared by extraction of MQ and internal standard from aqueous base with methyl tert.-butyl ether (MTBE), separation and evaporation of the MTBE layer, and derivatization using a solution of 9-fluorenylmethyl chloroformate in acetonitrile. Filter paper spots were immersed for 16 h in 0.1 M hydrochloric acid, followed by extraction with MTBE from aqueous sodium carbonate. The separated and evaporated organic layer was treated with the derivatizing solution. An aliquot was injected onto a high-performance liquid chromatography system using a C18 reversed-phase column and acetonitrile-water (72:28) mobile phase for filter paper spot extracts as for whole blood and urine extracts. The method has a limit of determination in blood, blood spots, and urine of 50 ng/ml with 100 microliters sample size (coefficient of variation = 16%). Linearity and precision (within-day and between-day) for the method are good. The MQ derivative was isolated and characterized spectroscopically. Values for MQ concentrations in filter paper blood spots compared favorably with values found in corresponding whole blood samples analyzed by a published method.
Chromatography, High Pressure Liquid↗
Efficacy of a loading dose of oral chloroquine in a 36-hour treatment schedule for uncomplicated plasmodium falciparum malaria.
The efficacy of a loading dose of 20 mg of chloroquine per kg of body weight per os given at intervals during the first day was evaluated in 27 patients in Madagascar with Plasmodium falciparum malaria. The conventional regimen of 25 mg/kg over 3 days (schedule 1) was thus compared with a regimen of 30 mg/kg over 2 days (schedule 2; one dose of 10 mg/kg followed by two doses of 5 mg/kg at 6-h intervals on the first day and two doses of 5 mg/kg at 12-h intervals on the second day) in terms of their clinical and parasitological efficacies, tolerance, and drug concentration-time curves. At 24 h schedule 2 gave higher chloroquine levels in blood, which induced a more rapid decrease in parasitemia. The time required for a 50% decrease in the initial parasitemia was shorter in patients on schedule 2 (14.3 +/- 1.6 h) than it was in patients on schedule 1 (35.5 +/- 5.4 h; P less than 0.01). Moreover, negative blood smears were obtained more rapidly with schedule 2 (50.8 +/- 3.7 h) than with schedule 1 (72 +/- 8.7 h). As predicted by the drug concentration-time curve, no high, potentially toxic peak drug concentration appeared and no adverse effects were observed with the loading dose regimen (schedule 2). These findings support the idea that a loading dose of 20 mg/kg given at intervals during the first 12 h is well tolerated and can be used to obtain a more rapid decrease in parasitemia and to shorten the treatment time of uncomplicated chloroquine-susceptible falciparum malaria in the field.
Administration, Oral↗
Standard and reduced doses of mefloquine for treatment of Plasmodium falciparum in Tanzania: whole blood concentrations in relation to adverse reactions, in vivo response, and in vitro susceptibility.
Fifty-three asymptomatic Tanzanian school children with 400-31,000 asexual Plasmodium falciparum parasites/microliter of blood were given standard, one-half, one-quarter, or one-eighth of the recommended mefloquine treatment dose of 25 mg base/kg body weight. Mefloquine and main metabolite concentrations were determined in 100 microliters of capillary blood using a high performance liquid chromatographic method. In the standard, one-half, and one-quarter dose groups, all children cleared the parasites within three days after treatment. Reappearance was noted in one of the children in the one-quarter dose group during 49-56 days of followup. Among the children given one-eighth of a dose, two had an RII response and four had an RI response with early recrudescence. All 24-hour in vitro micro-tests (n = 30) showed full susceptibility for mefloquine. Adverse gastrointestinal reactions were reported by eight children on the first day after treatment, four of whom had been given a standard dose. These children had higher mefloquine concentrations one day after treatment than the other children in this group (P less than 0.05). In the standard dose group (n = 13), the area under the curve of capillary whole blood concentrations of mefloquine versus time was 52.4-112.1 mumol/liter x days. The highest concentration on day 1 was 2.75-7.20 mumol/liter and the median terminal half-life was 17.4 days. The highest concentrations of the main metabolite were observed 1-2 weeks after treatment and the median half-life was 18.9 days. The concentrations in the other groups were approximately proportional to those in the standard dose group both for mefloquine and the metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Evaluation of test sensitivity and test specificity of three field methods for quantification of chloroquine in urine using liquid chromatography as reference method.
We have evaluated three quantitative colorimetric methods [bromthymol blue (BTB), Haskins, and Saker-Salomons (S-S)] for measurement of concentrations of chloroquine (CQ) in urine. A graphical evaluation of test sensitivity and test specificity at different concentrations of CQ in authentic urine samples was used. Liquid chromatography (LC) was used as a reference method. The Haskins method showed the highest test specificity (89%) and test sensitivity (97%), at a discrimination value of 2 mumols/L. At the same sensitivity (97%) as the Haskins method, S-S and BTB methods had test specificities of 49 and 13%, respectively. The correlation coefficients between the LC method and the colorimetric methods were all higher than 0.94 at a urinary concentration range of 2-100 mumols/L. The intra- and interassay variations for the colorimetric methods were all uniformly less than 15% at 2 mumols/L, but the Haskins method showed less variation than the other two methods.
Child↗
Improved sample collection technique for capillary blood on filter paper for determination of glycated haemoglobin.
A simple and practical method of sampling capillary blood was tested. This method was used for determination of glycated haemoglobin by ion exchange chromatography. Capillary blood was collected onto filter paper and placed in a small polypropylene tube containing phosphate-buffered sodium chloride with EDTA and p-hydroxybenzoic acid methyl ester. There was good correlation between filter paper sampling and conventional sampling in tubes with EDTA as anticoagulant. With this new sampling technique the glycated haemoglobin value was stable for 7 days at room temperature and for at least 10 days at +4 degrees C. Sampling can be performed by the patient at home and the sample then mailed to the laboratory, thus enabling analysis to be performed prior to the patient's visit to the physician.
Blood Specimen Collection↗
Total protein determined in human breast milk by use of coomassie brilliant blue and centrifugal analysis.
This simple method of centrifugal analysis for total protein in human breast milk is based on the change in the wavelength of the absorbance maximum of Coomassie Brilliant Blue G-250 when the dye is bound to protein. Within-run and between-day CVs were 3.8% and 4.8%, respectively. Compared with a micro-Kjeldahl method for determination of total nitrogen, the coefficient of correlation was 0.99.
Adult↗
Simplified analysis for glycated hemoglobin by ion-exchange chromatography.
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Chromatography, Ion Exchange↗
Detection and determination of antimalarial drugs and their metabolites in body fluids.
This review of methods for determining antimalarial drugs in biological fluids has focused on the various analytical techniques for the assay of chloroquine, quinine, amodiaquine, mefloquine, proguanil, pyrimethamine, sulphadoxine, primaquine and some of their metabolites. The methods for determining antimalarials and their metabolites in biological samples have changed rapidly during the last eight to ten years with the increased use of chromatographic techniques. Chloroquine is still the most used antimalarial drug, and various methods of different complexity exist for the determination of chloroquine and its metabolites in biological fluids. The pharmacokinetics of chloroquine and other antimalarials have been updated using these new methods. The various analytical techniques have been discussed, from simple colorimetric methods of intermediate selectivity and sensitivity to highly sophisticated, selective and sensitive chromatographic methods applied in a modern analytical laboratory. Knowledge concerning the method for a particular study is determined by the type of application and the facilities, equipment and personnel available. Often is it useful to apply various methods when conducting a clinical study in malaria-endemic areas. Field-adapted methods for the analysis of urine samples can be applied at the study site for screening, and corresponding blood samples can be preserved for subsequent analysis in the laboratory. Selecting samples for laboratory analysis is based on clinical, parasitological and field-assay data. The wide array of methods available for chloroquine permit carefully tailored approaches to acquire the necessary analytical information in clinical field studies concerning the use of this drug. The development of additional field-adapted and field-interfaced methods for other commonly used antimalarials will provide similar flexibility in field studies of these drugs.
Antimalarials↗
High-performance liquid chromatographic assay for the simultaneous monitoring of mefloquine and its acid metabolite in biological samples using protein precipitation and ion-pair extraction.
A high-performance liquid chromatographic (HPLC) method is presented for the simultaneous determination of mefloquine and its acid metabolite in plasma and whole blood. Plasma and whole blood are deproteinized with a combination of zinc and acetonitrile before extraction. Mefloquine and its acid metabolite are extracted simultaneously at pH 4 by methyl tert.-butyl ether, where mefloquine is extracted as an ion pair with heptanesulphonate. After evaporation of the organic phase, the residue is dissolved in mobile phase and injected on to the chromatographic column. A reversed-phase column (Spherisorb ODS-1) is used with acetonitrile-phosphate buffer (0.1 mol/l, pH 2.5) (42:58) containing 40 mmol/l perchlorate as the mobile phase. N,N-Dioctylamine was added to the mobile phase to give a concentration of 0.1% and the pH was adjusted to 2.3-2.7 with concentrated phosphoric acid. The method permits the determination of 0.10 mumol/l (30 ng/ml) mefloquine and its acid metabolite in plasma. The coefficient of variation was 5-6% at the therapeutic level (mefloquine 1-4 mumol/l, its carboxylic metabolite 2-6 mumol/l) in 0.5-ml samples. An alternative method is also described with a similar clean-up procedure that uses protein precipitation with zinc-acetonitrile as a sample pretreatment for therapeutic monitoring of mefloquine and metabolite in plasma and whole blood. Using this method, 0.25 mumol/l mefloquine and its metabolite can be determined. The results from the two methods correlate well.
Animals↗
Determination of mefloquine by electron-capture gas chromatography after phosgene derivatization in biological samples and in capillary blood collected on filter paper.
Mefloquine is determined in 100-microliter samples of whole blood, plasma and capillary blood collected on filter paper by gas chromatography with electron-capture detection after derivatization with phosgene. Sample preparation for whole blood and plasma involves a protein precipitation step that uses a combination of zinc and acetonitrile, followed by simultaneous extraction with methylene chloride and derivatization with phosgene at pH 9.50. Filter paper spots are immersed for 12-24 h in 0.1 M hydrochloric acid, followed by simultaneous extraction with methyl tert.-butyl ether and derivatization. After evaporation of the organic phase and reconstitution with ethyl acetate, 1 microliter of the extract is injected into a megabore capillary column. Because of the high sensitivity of the method, mefloquine concentrations down to 25 nmol/l (9.5 micrograms/l) are determined in 100-microliters samples with a relative standard deviation of 12% at the 25 nmol/l level. Excellent precision was obtained over the range of concentrations tested, 0.10-3 mumol/l (45-1100 micrograms/l), in both plasma and whole blood and from filter-paper-collected capillary blood. The day-to-day relative standard deviation in plasma at the therapeutic level (1-3 mumol/l) was 4.5% (n = 8).
Antimalarials↗
High-performance liquid chromatographic separation and extraction investigation for the simultaneous determination of mefloquine and its carboxylic acid metabolite.
Distribution ratios of mefloquine ion pairs with perchlorate and heptanesulphonate as counter-ions, the base distribution for mefloquine, the acid distribution for the carboxylic acid metabolite and the ion-pair distribution with quaternary ammonium ions as counter ions have been determined. Differences in retention characteristics with several commercially available supports bearing the same octadecyl label were found. The effect on the retention time of the pH, the percentage acetonitrile and the addition of an amine to the mobile phase were studied. Other antimalarial drugs present concurrently in the sample showed no chromatographic interference with mefloquine and its metabolite. A suitable internal standard for use in the analytical method was also tested.
Amines↗
An improved flow injection method for determination of lactate during exercise studies.
An improved enzymatic fluorometric method for automated analysis of lactate in perchloric acid extracts of capillary blood with flow injection (FIA) is described. The concentrations of lactate can be measured in as little as 20 microliter capillary blood from an exercising person. Within-day and between-day coefficients of variation are about 2%. The recovery of lactate from whole blood is 101%. Lactate is stable in perchloric acid extracts for at least 15 days at room temperature, and at +4 degrees C at least 30 days. Blank fluorescence in perchloric acid extracts of blood is low with the improved method. The FIA system is simple to use, inexpensive to operate, and is recommended for any laboratory with a high throughput of samples.
Autoanalysis↗
A high-performance liquid chromatographic method for determination of hypoxanthine in cord plasma.
A reversed-phase high-performance liquid chromatographic method was developed for the analysis of hypoxanthine in cord plasma. Cord plasma was precipitated with ammonium sulphate and after centrifugation the supernatant was injected into the chromatographic system. Separation of hypoxanthine was optimal with phosphate buffer (20 mmol/l, pH 7.65-7.75) as the mobile phase. Limit of determination using 200 microliter of the sample was found to be 1 mumol/l with a coefficient of variation of less than 10%. The imprecision of this method at the 10 mumol/l level was about 2%. The method described in this report for determination of hypoxanthine in cord plasma would also be suitable for determination of hypoxanthine in other biological fluids in clinical investigations. We have also determined reference values for hypoxanthine in citrate-preserved cord plasma. Rigorous sampling conditions and sample handling are important to achieve accurate results.
Chromatography, High Pressure Liquid↗
Parenteral chloroquine for treating falciparum malaria.
There is no information and therefore no consensus on how chloroquine should be administered to persons with severe malaria. Although widely considered dangerous, parenteral chloroquine is extensively used. We studied the acute disposition and toxicity of intravenous (iv), intramuscular (im), subcutaneous (sc), and oral chloroquine in 60 adult Zambian patients hospitalized with falciparum malaria. Plasma concentration profiles after parenteral administration were characterized by wide fluctuations between peak and trough values. Absorption of im and sc chloroquine was rapid, with a median time to peak concentration of 30 min and a peak plasma concentration five times higher than after oral administration. The pharmacokinetic data suggest that the acute toxicity of parenteral chloroquine is related to transiently high concentrations in blood and result from incomplete distribution out of a relatively small central compartment. Parenteral chloroquine may be administered safely by simply giving smaller, more-frequent doses than are currently used or, in the case of iv administration, by using continuous infusion.
Administration, Oral↗
Sulfadoxine assay using capillary blood samples dried on filter paper--suitable for monitoring of blood concentrations in the field.
A high performance liquid chromatographic method for determination of sulfadoxine in whole blood obtained by finger prick and dried on filter paper is presented. The technique was validated by comparing the sulfadoxine concentration of simultaneously collected capillary blood dried on filter paper and conventional venous whole blood samples. Agreement between capillary blood dried on filter paper and venous whole blood was satisfactory. Limit of determination using 100 microliter of capillary blood was found to be 25 mumol/L (7.8 micrograms/ml). Sulfadoxine was stable in the dried filter papers for at least 15 weeks at +37 degrees C. The concentration ratio between plasma and whole blood of sulfadoxine was found to be approximately 1.8. The sampling technique on filter paper offers a convenient method for overcoming many of the practical problems of blood sampling in the field.
Capillaries↗
Chloroquine and desethylchloroquine concentrations during regular long-term malaria prophylaxis.
The concentrations of chloroquine and desethylchloroquine in the blood of 10 healthy adult Swedish volunteers who had been taking 310 mg chloroquine base once a week for at least 8 months for malaria prophylaxis were measured. Samples of capillary whole blood from the volunteers were dried on filter-paper and the drug and its principal metabolite determined by a specific high-performance liquid chromatography (HPLC) method. The day after taking the drug, the mean concentration of chloroquine and desethylchloroquine in whole blood were 1305 nmol/l and 915 nmol/l, respectively, and immediately before the next weekly dose, 489 nmol/l and 384 nmol/l, respectively. These are considered to be greater than the minimum inhibitory concentrations for susceptible strains but less than the maximum tolerated concentrations. The dosage of chloroquine recommended roughly 40 years ago for regular long-term prophylaxis should therefore not be changed.
Adult↗
Accidental overdose of pyrimethamine and sulphadoxine for malaria prophylaxis without adverse effects.
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Antimalarials↗