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Biomedical subjects

P M Edelbroek

Publications and source records attributed to P M Edelbroek.

40 records · Page 3Linked to original sources

Determination of 8-methoxypsoralen in suction-blister fluid and serum by liquid chromatography.

A method is described for determination of 8-methoxypsoralen to 0.2 mL of suction-blister fluid or 1 mL of serum from psoriatic patients being treated with this drug. The drug is extracted from the biological matrix at pH 9.0 with a mixture of dichloromethane and light petroleum ether. 5-Methoxypsoralen is used as internal standard. Separation and quantitation are performed on a "high-performance" liquid chromatograph with use of an RP 18 reversed-phase column and detection at 245 nm. Accuracy and precision are good. Some benzodiazepines and their metabolites interfere. The lowest detectable concentration is 10 microgram/L, which means that the method is sufficiently sensitive to measure the drug concentrations in serum and suction-blister fluid for pharmacokinetic studies in patients being treated with a therapeutic dosage.

Blister↗

Improved micromethod for determination of underivatized clonazepam in serum by gas chromatography.

We describe a gas-chromatographic micromethod, with use of a solid injection system and an electron capture detector, for determination of underivatized clonazepam in serum. Vigorous mixing of 100 microliter of serum with 20 microliter of borate buffer (pH 9.0) and 100 microliter of a cyclohexane/dichloromethane mixture (4/6 by vol) containing methyl nitrazepam as internal standard suffices to extract 86% of the clonazepam into the organic layer. We obtained a linear response curve for clonazepam in serum in the concentration range 5 to 150 microgram/liter. The lowest detectable concentration by our method is about 1 microgram/liter of serum. Interference by several anticonvulsant drugs, metabolites, and related compounds was investigated. The assay is simple, rapid, and suitable for clinical routine determination of clonazepam in serum in therapeutic concentrations. We illustrate the steady-state concentration of clonazepam in serum during chronic oral administration to 28 patients.

Benzodiazepinones↗

Determination of nanogram levels of the anticoagulant acenocoumarin in serum by high-performance liquid chromatography.

A simple, rapid, and sensitive method for the determination fo the short-acting coumarin anticoagulant acenocoumarin in human serum is described. This drug is estracted from the acidified biological matrix together with the internal standard 5-methoxypsoralen. Separation and quantitation are performed on a high-performance liquid chromatograph with a reversed-phase column and an ultraviolet detector operating at 308 nm. Accuracy and precision are good. The lowest limit of detection is 15 microgram/L, which means that acenocoumarin concentrations can be measured in serum from the subtherapeutic to the toxic range. This method can also be used for rapid measurement of warfarin serum concentrations.

Acenocoumarol↗

Carbamazepine (CBZ) controlled release compared with conventional CBZ: a controlled study of attention and vigilance in children with epilepsy.

To compare the effects on attention and vigilance of conventional carbamazepine (CBZ) and CBZ controlled release (CBZ-CR), 15 schoolchildren with epilepsy and normal intelligence receiving CBZ were switched to CBZ-CR. Psychological examination was performed on the day before (day A) and 1 month after substitution (day B). Measurements of attention and vigilance were repeated throughout the day at 2-h intervals. Both on days A and B, CBZ plasma levels were monitored during a 12-h period. Fifteen matched healthy controls were submitted to identical test programs, allowing comparisons within subjects as well as between patients and control children. Variability of performance over sessions was neither increased nor decreased with CBZ-CR. Consistent differences over sessions did not exist between patients and controls with either drug. No relation was noted between reaction time and CBZ plasma level. The pharmacologic data confirm results of earlier studies in children. We noted a reduction in intradose fluctuations of CBZ level with CBZ-CR as compared with conventional CBZ. The neuropsychological results do not show a difference between the drugs. Neither were differences noted with respect to antiepileptic efficacy and side effects. At the end of the study, all but one of the children (and their parents) opted to receive CBZ-CR for ease of dosage administration and overall satisfaction.

Adolescent↗