Evaluation of the impurity profile of alcuronium by means of capillary electrophoresis.

Alcuronium, a neuromuscular blocking drug, was recently introduced to the European Pharmacopoeia. A HPLC method is described to limit the impurities of alcuronium, namely the diallylcaracurine (DAC) and the allyl-Wieland-Gumlich-aldehyde (WCA), to less than 0.5%. Since alcuronium and all impurities are quaternary salts, capillary electrophoresis (CE) is highly suitable to evaluate the impurity profile. Using 12 mM heptakis-(2,6-di-O-methyl)-beta-cyclodextrin in a 50 mM phosphate buffer at pH 5.5 or 50 mM diethanolamine buffer (pH 9.2)-acetonitrile 19:1 containing heptakis-(2,3-O-diacetyl-6-sulfo)-beta-cyclodextrin the impurities could be baseline separated and quantified. The limit of detection for DAC and WCA was found to be in the same range as found with HPLC; thus, less than 0.1% of both DAC and WCA could be detected in the solution for injection in presence of alcuronium. In injection solutions of alcuronium which were stored at higher temperatures three additional, unidentified impurities were detected. In addition, the conversion of alcuronium to DAC, occurring under acidic condition, was monitored by means of the CE method developed.

Simple and rapid high-performance liquid chromatography method for the determination of alcuronium in human plasma and urine.

A simple and quick HPLC assay for alcuronium is presented. Its characteristics are: precipitation of plasma proteins by acetonitrile; Spherisorb 5-CN column; acetonitrile-water (46:54, v/v) as mobile phase; flow-rate 1 ml/min; laudanosine 0.06 mg/l as internal standard with plasma; external standard with urine; UV detection at 294 nm; retention time 5.4 min; detection limit 0.025 mg/l; documented linearity: 0.025-2.0 mg/l for plasma and 1.0-80 mg/l for urine; intra- and inter-assay variability below 4%. None of nine drugs used in perioperative pharmacotherapy interfered with the assay. Satisfactory performance was exemplified in a 12-h pharmacokinetic evaluation of two patients.

Atracurio mas alcuronio en anestesia / Atracurio and alcuronio in anesthesia

Con el presente trabajo se busca demostrar los beneficios del ejemplo alternado en un mismo paciente de dos relajantes musculares no despolarizantes, en este caso atracurio y alcuronio, obteniendose condiciones optimas mas o menos rapidas de intubacion endo-traqueal, adecuada relajacion quirurgica, sin la necesidad de revertir a estos relajantes al finalizar el acto quirurgico. Disminuyendo de esta forma la dosis total de ambos relajantes, probabilidad de depresion respiratoria por relajacion residual post anestesica.

Persistence of allergy to anaesthetic drugs.

Intradermal testing and RIA testing for specific IgE antibodies to neuromuscular blocking drugs (NMBDs) were performed in patients referred to an Anaesthetic Allergy Clinic. Six patients were initially investigated four to 29 years after clinical anaphylaxis during anaesthesia and two of these patients and sixteen others were investigated by intradermal testing on two occasions at least four years apart. Seven patients had RIA tests for NMBD-specific IgE antibodies on two occasions at the time of skin testing. In all but two patients the evidence for drug-specific antibodies persisted 4-29 years after the reactions. In one patient all tests became negative and in another the skin test became negative but the positive RIA persisted. Evidence of antibodies to NMBDs persisted in 21 of 22 patients who had had anaphylactic reactions to these drugs during anaesthesia. In the absence of evidence of allergy diminishing with time in the majority of patients it would seem wise to avoid drugs responsible for reactions for the rest of the patient's life.