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Biomedical subjects

R A de Zeeuw

Publications and source records attributed to R A de Zeeuw.

At least 19 recordsLinked to original sources

Application of Empore C-8 extraction disks for screening urine in systematic toxicological analysis.

Solid-phase extraction (SPE) by means of disposable columns has become a widely accepted technique for sample pretreatment in toxicology, both for directed analyses and for screening analyses. However, the sample capacity in SPE is usually limited to a few millilitres. Therefore, we have investigated to what extent these problems can be overcome by using Empore extraction disks, consisting of chemically modified C-8 reversed-phase silica, embedded in an inert polytetrafluoroethylene (PTFE) matrix. Human urine was selected as the matrix and dexetimide and mepyramine were initially used as test drugs because these drugs were available in tritiated form. Additional drugs investigated included codeine, hexobarbital, imipramine, methamphetamine, and nitrazepam. In these investigations, the sample capacity for untreated urine was at least 25 mL, and analyte quantities up to 250 micrograms could be retained by these filters. Washing with water/methanol mixtures was successful in removing substantial amounts of endogenous interferences, and methanol proved to be an acceptable eluent. Thus, these disks seem to have interesting potential for toxicological analysis in that sample concentration and cleanup can be achieved at the same time.

Barbiturates

Isolation and determination of quaternary ammonium compounds by means of amberlite XAD-columns and thin layer chromatography.

The potentials of XAD-columns for the isolation of quaternary ammonium compounds from aqueous media have been investigated. When adequate amounts of counter ions (perchlorate, chloride, phosphate, nitrate) were added to the aqueous sample, to the column pretreatment fluid and to the aqueous washing fluid, most quaternary compounds investigated were retained on the column and could be recovered by elution with methanol. This approach proved also suitable for urine. Quantitation of quaternaries isolated in this way from urine samples could be performed on silicagel thin layer plates through visualization with iodine, followed by densitometric evaluation. For decamethonium detection limits were 0.1 micrograms/ml. Recoveries at the 1 micrograms/ml level were between 80--90% with variation coefficients of less than 10%.

Chromatography, Ion Exchange

First-pass effect after rectal administration of thiazinamium methylsulfate.

The absorption and metabolism of the quaternary ammonium compound thiazinamium methylsulfate were studied in humans using plasma concentration data and urinary excretion measurements. After giving a dose of 150 mg in suppositories, the relative bioavailability was 5.8 +/- 3.2 (SD) % of the dose, comparable to the values obtained following oral administration. The degree of first-pass effect observed after rectal administration was comparable with that after oral administration.

Aged

An unusual case of carbamazepine poisoning with a near-fatal relapse after two days.

A severe case of carbamazepine is described in which the drug and its major metabolite were monitored by means of HPLC. After 2 days of treatment a dramatic rise in plasma concentration of carbamazepine and its metabolite was observed, accompanied by a relapse into deep coma, then followed by a rapid elimination of the drugs and complete recovery within 4 days. The possible mechanisms underlying these phenomena and potential therapeutic measures are discussed.

Adult

Isolation and determination of quaternary ammonium compounds by means of XAD-columns and thin layer chromatography.

The potentials of XAD-columns for the isolation of quaternary ammonium compounds from aqueous media have been investigated. When adequate amounts of counter ions (perchlorate, chloride, phosphate, nitrate) were added to the aqueous sample, to the column pretreatment fluid and to the aqueous washing fluid, most quaternary compounds investigated were retained on the column and could be recovered by elution with methanol. Quantitation of decamethonium isolated in this way from urine samples could be performed on silicagel thin layer plates through visualization with iodine, followed by densitometric evaluation. Detection limits were 0.1 microgram/ml. Recoveries at the 1 microgram/ml level were between 80-90% with variation coefficients of less than 10%.

Chromatography

An unusual case of carbamazepine poisoning with a near-fatal relapse after two days.

A severe case of carbamazepine is described in which the drug and its major metabolite were monitored by means of HPLC. After two days of treatment a dramatic rise in plasma concentration of carbamazepine and its metabolite was observed, accompanied by a relapse into deep coma, then followed by a rapid elimination of the drugs and complete recovery within 4 days. The possible mechanisms underlying these phenomena and potential therapeutic measures are being discussed.

Adult

Kinetics of carbamazepine and carbamazepine-epoxide, determined by use of plasma and saliva.

The concentration-time curves of carbamazepine (CBZ) and its metabolite (carbamazepine-10,11-epoxide; CBZ-epoxide) were determined in patients undergoing long-term antiepileptic drug treatment with the use of plasma and saliva data. Plasma and saliva samples were assayed concurrently for each patient by liquid chromatography. There was excellent linear correlation between CBZ levels in saliva and plasma (r = 0.991, p less than 0.001) over a large concentration range. The saliva/plasma ratio for CBZ concentration was 0.26 +/- 0.01 (SD). Since CBZ binding to plasma proteins is in the order of 76%, saliva CBZ concentration seems to reflect the unbound fraction of the drug in plasma. CBZ-epoxide has not been detected in saliva. The pharmacokinetic parameters of CBZ-epoxide were determined in 6 patients. The pharmacokinetic parameters of CBZ obtained from saliva concentrations were in excellent agreement with those obtained from plasma concentrations. Thus, CBZ determination in saliva is convenient for controlling blood levels in patients as well as for studying pharmacokinetics. The half-life, the relative body clearance of CBZ, and the metabolite concentration during steady-state, expressed as percent the parent compound, appear to be significantly different in patients on single and combined drug therapy.

Adolescent

Determination of oxyphenonium bromide in plasma and urine by means of ion-pair extraction, derivatization and gas chromatography-electron-capture detection.

A sensitive and selective method for the determination of the quaternary ammonium compound oxyphenonium bromide (Antrenyl), a drug with strong anticholinergic properties, in human plasma and urine is described. The method is based on ion-pair extraction of the cation with perchlorate, a re-extraction according to ion-pair principles with tetrapentylammonium as the counter ion, hydrolysis to cyclohexylphenylglycolic acid, derivatization of this acid to its pentafluorobenzyl ester and determination of the ester by gas chromatography and electron-capture detection. Quantitation is possible down to 2 ng/ml of oxyphenonium bromide using 1 ml of plasma and down to 200 ng/ml using 0.1 ml of urine. The method described can also be applied to other anticholinergic drugs with an ester function.

Animals

Determination of clomipramine and desmethylclomipramine in plasma by means of liquid chromatography.

A method is presented for the determination of clomipramine and its major metabolite desmethylclomipramine in plasma. After extraction with n-hexane, the components are separated by high performance liquid-solid chromatography on silica gel and detected with a UV detector. The detection limits are 2 ng/ml for clomipramine and 10 ng/ml for desmethylclomipramine. Recoveries from plasma exceed 95% for both drugs. In routine analysis, 30-40 samples can be handled in one day. The practical use of the method is shown in plasma concentration-time curves after oral and intramuscular administration of clomipramine.

Chromatography, High Pressure Liquid

Relationship between carbamazepine concentrations in plasma and saliva in man as determined by liquid chromatography.

The concentration of carbamazepine in plasma and saliva was determined in 7 subjects receiving carbamazepine. Plasma and saliva samples were assayed was an excellent linear relationship between carbamazepine concentrations in saliva and plasma (r = 0.991, p less than 0.001) over a plasma concentration range of 0.2--8.0 microgram/ml. The saliva/plasma ratio for carbamazepine was 0.26 +/- 0.02 (S.D.). Since carbamazepine binding to plasma proteins is in the order of 75%, the saliva concentration seems to reflect the concentration of the free drug in plasma. There is very little intrasubject and intersubject variation in the concentration ratio of carbamazepine. This study demonstrates that carbamazepine determination in saliva is a convenient method for optimizing blood levels of patients as well as for the study of pharmacokinetic properties.

Carbamazepine

Analytical problems with putrefaction in a fatal case involving ergotamine and pentazocine.

A 29-year-old male drug addict was found dead at the bottom of a staircase. Analysis of the acid-hydrolized blood showed the presence of pentazocine and two characteristic compounds that contained L-phenylalanine and D-proline, linked together by peptide bounds. It was shown that the latter two components could emanate from the peptide part of ergotamine under the conditions used. It seemed likely that, at the time of analysis, pentazocine and ergotamine were present at concentrations far above therapeutic values. A third component in the blood could not be identified.

Adult

Differential pulse anodic stripping voltammetry as a rapid screening technique for heavy metal intoxications.

This paper describes a relatively simple and rapid analytical procedure capable to carry out systematic screening for 10 heavy metals, namely mercury, bismuth, antimony, copper, lead, tin, thallium, indium, cadmium and zinc. Differential pulse anodic stripping voltammetry was chosen because of its simplicity, speed, low cost, low detection limits, screening potential for a wide selection of metals and the combined qualitative and quantitative output. The method of identification is based on measuring peak potentials in 2 different types of electrolyte solution, using 2 different electrodes. Complexing agents are used to mask certain elements.

Electrodes

Rapid and sensitive liquid chromatographic determination of carbamazepine suitable for use in monitoring multiple-drug anticonvulsant therapy.

A rapid, sensitive and selective method for the determination of carbamazepine and its major metabolite in plasma has been developed. Other commonly used anticonvulsants can be determined in the same procedure without interference. After extraction with dichloromethane, the components are separated by high-pressure liquid chromatography without further clean-up or concentration on a column packed with small-particle silica gel. The mean recovery from plasma is 98.6% with a relative standard deviation of 1.6%. The detection limit for carbamazepine is approximately 2 ng/ml, requiring 1 ml of plasma.

Carbamazepine

A rapid and specific method for the determination of traces of thallium directly in urine by differential pulse anodic stripping voltammetry.

The applicability of differential pulse anodic stripping voltammetry to the direct qualitative and quantitative analysis of thallium in urine has been investigated. Comparisons were made between the hanging mercury drop electrode and the mercury plated wax impregnated graphite electrode. The latter electrode was found to be somewhat more sensitive, with detection limits in the lower ppb range. For quantitative determination, the hanging mercury drop electrode showed better reproducibility. The effects of toxicologically important metals on the analysis of thallium were investigated and their possible interference could be eliminated by a proper choice of operating conditions. The advantages of the proposed method are its sensitivity, speed and low cost in comparison with other methods for detecting and measuring thallium.

Electrodes

Determination of low cencentrations of the quaternary ammonium compound thiazinamium methylsulphate in plasma and urine.

A sensitive and selective method for the quantitative determination of the quaternary ammonium antiacetylcholine-compound thiazinamium methylsulphate (Multergan) in plasma and urine is described. The procedure is based on ion pair extraction of the compound with iodide as the counter ion. This is followed by gas chromatography using an alkali flame ionization detector. The detection limit is 2 ng ml-1 with a recovery of 88-0 +/- 6-2% from plasma, 91-4 +/- 4-6% from urine. The described method can also be applied to other quaternary ammonium compounds.

Chromatography, Gas