Impurity profiling of carbocisteine by HPLC-CAD, qNMR and UV/vis spectroscopy
Oliver Wahl, Ulrike Holzgrabe
文献索引:J. Pharm. Biomed. Anal. 95 , 1-10, (2014)
全文:HTML全文
摘要
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.Copyright © 2014 Elsevier B.V. All rights reserved.
相关化合物
相关文献:
2014-01-01
[PLoS ONE 9(10) , e108408, (2014)]
2015-01-01
[PLoS ONE 10(3) , e0120746, (2015)]
2015-04-30
[Carbohydr. Res. 407 , 131-6, (2015)]
2015-03-01
[Diabetologia 58(3) , 596-603, (2015)]
2015-04-10
[Carbohydr. Res. 406 , 19-26, (2015)]