Bestimmung von Alkylsulfonsäureestern in Mesilat- bzw. Besilatsalzhaltigen Arzneimitteln mittels GC/MS bzw. LC/MS Uwe Wollein, Nicholas Schramek Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Oberschleißheim Korrespondenz: Dr. Nicholas Schramek, Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Sachgebiet Pharmazie, Veterinärstr. 2, 85764 Oberschleißheim (Germany), e-mail: nicholas.schramek@lgl.bayern.de Determination of Esters of Alkylsulfonic Acid in Mesylate or Besylate Containing Medicinal Products Using GC/MS or LC/MS Methods The article describes the determination of potential genotoxic impurities that could occur during the manufacturing process of medicinal products. Especially the presence of esters of methanesulfonic acid (mesylates) and benzenesulfonic acid (besylates) has been screened and accordingly quantified. The analytes were extracted by liquid-liquid extraction after development of GC/MS and LC/MS methods. The “Guideline on the Limits of Genotoxic Impurities” which has been issued in 2007 by the European Medicines Agency (EMA) was the base for this evaluation. The guideline limits the daily intake of potential genotoxic impurities to 1.5 μg/person (according to a TTC (threshold of toxicological concern) of 1.5 μg/person/day). Within the range of 57 samples, only four showed a TTC higher than 1.5 mg, but depending on the directions of use. Because of current regulations and a very low TTC level, determination of genotoxic impurities is a significant challenge for control laboratories in pharmaceutical analysis. Key words GC/MS • Genotoxische Verunreinigungen • HPLC/MS • Sulfonsäureester • Threshold of toxicological concern (TTC) |
|
|
pharmind 2011, Nr. 3, Seite 574
