High-performance liquid chromatographic method for the simultaneous determination of pentisomide and its major metabolite N-desisopropylpentisomide in plasma, urine and tissues using solid-phase extraction.
A rapid, sensitive and selective high-performance liquid chromatographic method for the simultaneous determination of pentisomide and its major metabolite desisopropylpentisomide in plasma, urine and tissues has been developed. The method for plasma samples, urine samples and tissue samples, after homogenizing with 50% ethanol, involves extraction of samples via activated Bond-Elut C8 disposable columns with methanol at pH 10 after addition of internal standard, and initially on column washing of samples at pH 10 with water and acetonitrile. The obtained methanolic extract is evaporated to dryness under nitrogen at 25 degrees C; the sample residue is then reconstituted in mobile phase and an aliquot of this solution is injected into the liquid chromatograph. Separation is performed using a Nova-Pak C18 4 microns particle size column operating in combination with radial compression separation unit and a methanol-water-di-sec.-butylamine-phosphoric acid (40:60:0.5:0.2, v/v) pH 3.5 mobile phase with ultraviolet detection at 258 nm. Endogenous substances or a variety of drugs concomitantly used in pentisomide therapy, with the exception of disopyramide, do not interfere with the assay. The mean recovery of pentisomide and desisopropylpentisomide from plasma and urine and from tissues is more than 91 and 86%, respectively. The limit of detection of the assay is 10 ng/ml for both drugs. The intra- and inter-day coefficient of variation for replicate analyses of spiked plasma samples is less than 7 and 8%, respectively. Mean steady-state plasma levels of pentisomide and desisopropylpentisomide in patients on chronic oral therapy are reported.
Comparative effects of three class I antiarrhythmic drugs on plateau and pacemaker currents of sheep cardiac Purkinje fibres.
The electrophysiological effects of three class I antiarrhythmic drugs, lignocaine, disopyramide, and penticainide, were compared in sheep cardiac Purkinje fibres. Action potential duration was shortened with all three drugs, the effect being small with disopyramide, moderate with penticainide, and greatest with lignocaine. Slowing down of the early phase of repolarisation was greatest with disopyramide, smaller with penticainide, and did not occur with lignocaine. Automaticity recorded in low potassium media was unaltered (disopyramide), depressed (penticainide), or stopped (lignocaine). Ionic currents were recorded in short fibres using the two microelectrode voltage clamp technique. The tetrodotoxin sensitive slow component of the sodium current was suppressed (lignocaine) or reduced (penticainide and disopyramide) and the instantaneous background potassium current slightly reduced (disopyramide more than penticainide), unaffected, or slightly increased (lignocaine). The three drugs depressed moderately and similarly the slow inward calcium current. The amplitude of the 4-aminopyridine sensitive transient outward potassium current was almost unaffected (lignocaine) or appreciably depressed (disopyramide more than penticainide). The pacemaker current was reduced greatly by lignocaine, moderately by penticainide, and slightly by disopyramide. Changes in ionic currents may explain the effects of the three drugs on action potential plateau and automaticity of sheep Purkinje fibres. It is concluded that the pronounced differences observed in the effects of these three class I antiarrhythmic drugs on pacemaker depolarisation and on initial repolarisation may justify a more discriminative subdivision of class I antiarrhythmic drugs.
Preparation of cyanoacrylate derivatives and comparison of dual action cyanoacrylate formulations.
The use of cyanoacrylate followed by fluorescent reagents is well known in the field of fingermark visualisation. Treatment with fluorescent reagents that stain the cyanoacrylate deposits will not only enhance the visibility of fingermarks previously thought unusable, but also reveal previously unseen marks. Downside of this approach is the exposure of the evidential material to large amounts of solvent, such as water, methanol and ethanol, thereby potentially destroying other forensic traces. New cyanoacrylate derivates with fluorescent and UV-active properties can be used for one step dual action visualisation of latent fingermarks. Increased optical properties can be achieved by addition of functional groups via the Steglich esterification of cyanoacetic acid with N-(3-dimetylaminopropyl)-N'-ethylcarbodiimide (EDC). The UV-active ester can be created via the Knoevenagel condensation with formaldehyde to form poly-cyanoacrylate. These poly-cyanoacrylates can be depolymerised to form monomer cyanoacrylates. In this paper we compare these ethylcyanoacrylate derivatives with commercially available cyanoacrylate formulations. We have shown that the use of poly-cyanoacrylate derivatives can yield fully developed fingerprints. The initiator of the polymerisation reaction towards novel reagents can be altered according to the need for particular optical properties.