Biomedical subjects

D A Doornbos

Publications and source records attributed to D A Doornbos.

At least 19 recordsLinked to original sources

PubMed1993

Liquid chromatographic analysis of carboxylic acids using N-(4-aminobutyl)-N-ethylisoluminol as chemiluminescent label: determination of ibuprofen in saliva.

N-(4-Aminobutyl)-N-ethylisoluminol was used for labelling of carboxylic acids. The derivatization reaction was carried out with 1-hydroxybenzotriazole as pre-activator of the carboxylic acid function and N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide as the coupling reagent. Optimum conditions for the derivatization were determined by using factorial design analysis, with ibuprofen as the test compound. Chemiluminescence detection was carried out using a post-column on-line electrochemical hydrogen peroxide generation system and the addition of microperoxidase as the catalyst. The detection limit of derivatized ibuprofen in human saliva was 0.7 ng per 0.5 ml of saliva, with a recovery of 96.1 +/- 1.3%. The method was linear over at least three decades (2.5 ng to 2.5 micrograms) and the repeatability was satisfactory (R.S.D. = 5.2% at the 25 ng level; n = 4).

Blood Proteins↗

PubMed1993

Chemometrics in bioanalytical sample preparation. A fractionated combined mixture and factorial design for the modelling of the recovery of five tricyclic amines from plasma after liquid-liquid extraction prior to high-performance liquid chromatography.

A general systematic approach is described for the chemometric modelling of liquid-liquid extraction data of drugs from biological fluids. Extraction solvents were selected from Snyder's solvent selectivity triangle: methyl tert.-butyl ether, methylene chloride and chloroform. The composition of a mixture of the three extraction solvents was varied and the extraction yield (recovery) of a group of tricyclic amines was measured at all compositions selected. Two process variables, the extraction time and the extraction intensity, were varied simultaneously with the mixture variables to study their influence and their interaction with the mixture composition. The combined mixture and factorial design statistical techniques obtained in this way enabled the recovery to be modelled as a function of both the composition of the extraction liquid and the process variables. The models were assessed with regard to both descriptive and predictive capacities. The results showed that structurally related compounds may demonstrate different partitioning behaviour with regard to both mixture variables and process variables. It was concluded that mixtures of solvents result in higher extraction efficiencies for the amines. A positive effect on the extraction efficiency was demonstrated by the extraction intensity process variable and extraction time. A positive effect on the extraction efficiency was demonstrated by an interaction between extraction intensity and time. Mixture models in which process variables were introduced were recognized as being very suitable for modelling liquid-liquid extraction systems.

Antidepressive Agents, Tricyclic↗

PubMed1993

Partial least-squares regression for routine analysis of urinary calculus composition with Fourier transform infrared analysis.

Quantitative assessment of urinary calculus (renal stone) constituents by infrared analysis (IR) is hampered by the need of expert knowledge for spectrum interpretation. Our laboratory performed a computerized search of several libraries, containing 235 reference spectra from various mixtures with different proportions. Library search was followed by visual interpretation of band intensities for more precise semiquantitative determination of the composition. We tested partial least-squares (PLS) regression for the most frequently occurring compositions of urinary calculi. Using a constrained mixture design, we prepared various samples containing whewellite, weddellite, and carbonate apatite and used these as a calibration set for PLS regression. The value of PLS analysis was investigated by the assay of known artificial mixtures and selected patients' samples for which the semiquantitative compositions were determined by computerized library search followed by visual interpretation. Compared with that method, PLS analysis was superior with respect to accuracy and necessity of expert knowledge. Apart from some practical limitations in data-handling facilities, we believe that PLS regression offers a promising tool for routine quantification, not only for whewellite, weddellite, and carbonate apatite, but also for other compositions of the urinary calculus.

Apatites↗

PubMed1990

Development of a laboratory robotic system for automated bioanalytical methods--I. The determination of theophylline in human plasma: a comparison between the robotized and manual method.

The quality of bioanalytical methods is often determined by the quality of sample preparation. Using a robot for sample treatment may give better results than manual sample preparation, since the robot lacks human behaviour and incidental errors that are part of it. The use of a laboratory robot has the additional advantage of giving each sample the same analytical history, resulting in better reproducibility. An automated method has been developed for the analysis of drugs in plasma using a laboratory robot. Theophylline was used as a probe drug. Sample preparation was automated with a Zymate II robot, followed by separation and quantitation on an HPLC-system. The robotic method showed a good correlation with the manual method, while sample throughput was doubled.

Chemistry, Clinical↗

PubMed1990

Development of a laboratory robotic system for automated bioanalytical methods--II. A robot computer program for guarding totally automated bioanalytical methods.

The application of fully automated, unattended sample preparation performed by a laboratory robot for the analysis of drugs in biological samples requires the prevention of system failures which may arise in the on-line coupled chromatographic system or in other components of the robotic system. A computer program has been developed which can help to detect such problems. The control program for the robotic sample preparation contains a number of safety measures to intercept robotic or human errors. A routine is implemented, guarding for chromatographic malfunctions and errors in dispensing liquids by the robot. After detection of trouble, sample preparation is interrupted.

Algorithms↗

PubMed1987

Optimization of the reversed-phase high-performance liquid chromatographic separation of synthetic estrogenic and progestogenic steroids using the multi-criteria decision making method.

The optimization of the reversed-phase high-performance liquid chromatographic separation of a mixture of ethynylestradiol, desogestrel and three related compounds is described. A procedure is used that allows the prediction of the capacity factors of each individual synthetic steroid, depending on the mobile phase composition. Therefore, complete chromatograms can be predicted and evaluated with the multi-criteria decision making method.

Chromatography, High Pressure Liquid↗

PubMed1984

Development and optimization of pharmaceutical formulations using a simplex lattice design.

The composition of pharmaceutical formulations is often subject to trial and error. This approach is time consuming and unreliable in finding the best formulation. Optimization by means of an experimental design might be helpful in shortening experimenting time. Such a design with the concomitant mathematical models, reveals effects and interactions of the variables. The independent variables are the different compositions of the mixtures of the chosen ingredients [drug(s) and excipients]. The dependent variables are the properties (responses) of the formulation. When all responses of interest have been expressed in models that describe the response as a function of the composition of the mixture, the models can be combined graphically or mathematically to find a composition satisfying all demands. In this paper an introduction to the use of mixture designs will be given by means of a theoretical part and an example: optimizing a tablet formulation consisting of excipients only.

Chemical Phenomena↗

PubMed1984

Remarks on the structure-activity relationship of silver sulfanilamides.

The biological activity of a series of 10 silver sulfanilamides is studied in relation to the physical parameters pK alpha, log K, and the aqueous solubility. None of the parameters demonstrate a simple relationship with the activity. A discussion of the significance of log K and the solubility in relation to the activity is given.

Ointments↗

PubMed1983

Optimization of a novel two-phase potentiometric titration method of barbiturates with mercury (II). Part I: Theory.

A two-phase potentiometric titration procedure for barbiturates with mercury(II) was developed. In the new titration procedure the barbituric acid derivative is dissolved in an aqueous borate buffer. An organic phase consisting of chloroform and benzyl alcohol is added, and the vigourously stirred contents of the titration vessel are titrated by a mercury(II) nitrate solution. The theory of the conditional formation constant in a two-phase system is derived to provide a basis for the selection of optimal titration conditions. It is shown that the new conditional formation constant of the two-phase system, K, increases if the mercury-barbiturate complex is extracted into the organic layer. By extraction of the barbituric acid derivative into the organic layer K is diminished, but this effect can be minimized by a correct choice of the pH of the aqueous layer. The influence of these factors on the pM jump in the equivalence point is demonstrated by calculation of the corresponding theoretical titration curves.

Barbiturates↗

PubMed1983

Optimization of a novel two-phase potentiometric titration method of barbiturates with mercury (II). Part II: Experimental evaluation.

A two-phase potentiometric titration procedure of barbiturates with mercury(II) was developed. The composition of the formed mercury-barbiturate complexes was elucidated by infrared spectrometry. In the new titration procedure the barbituric acid derivative is dissolved in an aqueous borate buffer. An organic phase consisting of chloroform and benzyl alcohol is added, and the vigorously stirred contents of the titration vessel are titrated by a mercury(II) nitrate solution. In the potentiometric determination of the end-point a rotating mercury electrode is used as an indicator electrode that also serves as an efficient stirrer. The two-phase procedure was compared with a one-phase mercurimetric potentiometric titration in borate buffer and with the potentiometric titration by sodium hydroxide in an ethanol-water solution. The proposed two-phase procedure is superior to both methods because lower concentrations of barbiturates (10(-3) - 10(-4) M) can be determined successfully. The one-phase procedure suffers from systematic errors, while the titration with sodium hydroxide is less precise at concentration levels of the barbiturates prevailing in content uniformity studies. By the two-phase procedure the direct titration of phenobarbital and mephobarbital in a dry mix of tablet excipients was possible with a relative standard deviation smaller than 1.5 percent.

Barbital↗

PubMed1982

Reversed-phase high-performance liquid chromatographic separation of saccharin, caffeine and benzoic acid using non-linear programming.

A method is described which allows a chromatographic assay to be optimized with respect to the time needed to complete an analysis, while maintaining good resolution. The method introduces an operational research technique called linear programming. It was used to optimize the eluent composition for the assay of saccharin, caffeine and benzoic acid and resulted in a significant reduction in the analysis time.

Benzoates↗

PubMed1982

Microcomputer-controlled determination of dissociation constants of sulfanilamides and stability constants of the related silver complexes.

As a contribution to the structure-activity relationship of silver sulfanilamide complexes, the pKa-values of thirteen sulfanilamides and the log K-values of their related silver compounds were determined using a microcomputer-controlled titrator which determines the silver ion concentration and hydrogen ion concentration in a combined measurement. Predictions on antibacterial effectiveness and the risk of sensitization reactions of some of the investigated silver sulfanilamides are made on the basis of the conditional stability constants computed from the pKa- and log K-values at pH = 7.4.

Chemical Phenomena↗

PubMed1971