Biomedical subjects

K Ensing

Publications and source records attributed to K Ensing.

59 records · Page 4Linked to original sources

PubMed1982

Determination of mitomycin C in plasma, serum and urine by high-performance liquid chromatography with ultra-violet and electrochemical detection.

The performance of a number of normal phase and reversed-phase systems, with ultraviolet detection at 360 nm, has been investigated with respect to their applicability to pharmacokinetic studies of mitomycin C (MMC). The reversed-phase system developed was also combined with a polarographic detector in order to compare the sensitivity and selectivity of ultraviolet and electrochemical detection. A simple isolation procedure, based on the adsorption of MMC on a non-ionogenic resin, has been developed. The developed assay is applied to a pharmacokinetic study from which some examples are given.

Animals↗

PubMedDate not supplied

Pitfalls and solutions in the development of a fully automated solid-phase extraction method for drug screening purposes in plasma and whole blood.

A fully automated solid-phase extraction (SPE) method for drug screening is described. The extraction of 19 toxicologically relevant drugs from pretreated plasma and pretreated whole blood was accomplished automatically by a Gilson ASPEC system equipped with disposable 2.8-mL Bond Elut Certify columns. The automated extraction procedure includes 11 fundamental steps: column preconditioning; sample application; column washing; pH adjustment; elution of drugs by two eluents, which were collected into two separated tubes; addition of the chromatographic standard solution; and several SPE column rack movement steps. After evaporation, the drugs were quantitated by gas chromatography. Water was chosen as the transfer liquid in the ASPEC system because it was cheap and, more importantly, because it caused no protein precipitation problem. The effects of the sample and eluent flow rates were investigated, and it was found that low flow rates were necessary to recover the drugs maximally. In the study, the optimal flow rates of sample application, acetone-chloroform elution, and ammoniated ethyl acetate elution were 1.5, 0.72, and 0.33 mL/min, respectively. The absolute recoveries of 19 drugs from whole blood exceeded 82%, with relative standard deviations less than 5% at 2 micrograms/mL.

Blood Chemical Analysis↗

PubMedDate not supplied

Tuning of the selectivity in capillary electrophoresis by cyclodextrins illustrated by the separation of some structurally related phenothiazines.

Cyclodextrins were used to affect the selectivity of the capillary electrophoresis system in the separation of 10 widely used phenothiazines. It was shown that the addition of cyclodextrins substantially improved the selectivity. The effect of temperature and cyclodextrin concentration was studied on the resolution between the screened phenothiazines. The best results were obtained with 8 mM hydroxypropyl-beta-cyclodextrin at 15.5 degrees C. Under these conditions, a resolution of at least 1.5 between all phenothiazines could be obtained. In addition, the chiral separation of the enantiomers of trimeprazine could be accomplished. Structure separability relations between the phenothiazines showed that a change in the side chain at the R10 position had the greatest effect on the migration.

Cyclodextrins↗

PubMedDate not supplied

Heterogeneous receptor binding of classical quaternary muscarinic antagonists. II. Modulation in bovine brain.

The heterogeneous binding behavior exhibited by classical quaternary muscarinic antagonists was further investigated in order to establish possible molecular and/or environmental differences between the high (Q1) and low (Q2) affinity binding sites. Using agents that are known to modulate (muscarinic) receptor binding (Na+ and Mg2+, 5'-guanylylimido diphosphate, dithiothreitol, N-ethylmaleimide), no evidence was obtained that the Q1 and Q2 binding site populations are molecularly different muscarinic receptor subtypes. Using membrane modulating agents (sodium dodecyl sulphate, digitonin, polyethylene glycol 6000, cholesteryl hemisuccinate), no evidence was obtained that the Q2 binding site population represents muscarinic receptors located in a different membrane environment less accessible to quaternary compounds. However, a qualitative correlation was found between lipid solubility and the appearance of Q1/Q2 binding heterogeneity for six quaternary muscarinic antagonists, suggesting that the low affinity binding sites may be (normal) muscarinic receptors located in a hydrophobic membrane domain.

Animals↗

PubMedDate not supplied

Heterogeneous receptor binding of classical quaternary muscarinic antagonists. I. Bovine tissue distribution.

In competition experiments with the tertiary radioligand [3H]dexetimide, classical quaternary muscarinic antagonists like ipratropium bromide and N-methylscopolamine bromide distinguished two muscarinic binding sites in bovine brain (total brain minus cerebellum) membranes, in contrast to their tertiary analogues, atropine and scopolamine, which recognized only one binding site. This binding behavior was found to be almost identical in bovine striatal membranes, both in terms of binding affinities and proportions of high (Q1) and low (Q2) affinity binding sites. Both in total brain and in striatal membranes, the Q1/Q2 binding heterogeneity was independent of pirenzepine binding heterogeneity (M1/M2). In peripheral tissues, the binding properties of quaternary muscarinic antagonists varied. Whereas tertiary as well as quaternary compounds showed only high affinity binding towards muscarinic receptors in bovine atrial and left ventricular membranes, heterogeneous binding behavior was observed with quaternary but not with tertiary antagonists in bovine tracheal smooth muscle membranes. The tissue distribution found in the present study suggests that bovine tracheal smooth muscle contraction studies might shed light on the functional significance of the anomalous binding behavior of quaternary muscarinic antagonists.

Animals↗