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

Maike Wedig, Nikolai Novatchev, Tina Worch, Stefanie Laug, Ulrike Holzgrabe

Index: J. Pharm. Biomed. Anal. 28(5) , 983-90, (2002)

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Abstract

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.