title: Impurity profiling of carbocisteine by HPLC-CAD, qNMR and UV/vis spectroscopy.
abstract: For the impurity profiling of the mucolytic and anti-inflammatory drug carbocisteine a high performance liquid chromatographic (HPLC) method using corona charged aerosol detection (CAD) was developed and fully validated following the ICH guideline Q2(R1). The response was linear (R²>0.995) over a small concentration range (0.05-0.25 or 0.10-0.60% respectively) and a detection limit of at least 0.03% was registered. The separation was achieved on a mixed mode column combining hydrophobic C18 and strong cation exchange retention mechanisms using a mass spectrometer compatible volatile mobile phase consisting of trifluoroacetic acid 10 mM and acetonitrile 12% (V/V). Impurities, not assessable by HPLC-CAD such as the volatile chloroacetic acid and the unstable cysteine, were determined by quantitative NMR (qNMR) with maleic acid as internal standard and UV/vis spectroscopy after reaction with Ellman's reagent, respectively. Six batches of three different manufacturers were tested by means of those methods. The purity varied from below 99.0 to higher than 99.8 per cent. The major impurities of all batches were the starting material cystine and N,S-dicarboxymethylcysteine being a synthesis by-product.
authors.affiliation: University of Würzburg, Institute for Pharmacy and Food Chemistry, 97074 Würzburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Wahl
authors.affiliation: University of Würzburg, Institute for Pharmacy and Food Chemistry, 97074 Würzburg, Germany. Electronic address: u.holzgrabe@pharmazie.uni-wuerzburg.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
mesh_terms: D002233:Carbocysteine / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004340:Drug Contamination; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
chemical_list: D002233:Carbocysteine
keywords: Amino acids; Carbocisteine; Corona charged aerosol detector; Impurity stability; Pharmaceutical analysis