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Almeling S.,European Directorate for the Quality of Medicines and Health Care | Holzgrabe U.,University of Wurzburg
Journal of Chromatography A | Year: 2010

High performance liquid chromatography (HPLC) with evaporative light scattering detection (ELSD) is a versatile, easy to use and inexpensive alternative when it comes to the analysis of substances lacking a chromophor for UV detection. However, in pharmaceutical analysis injection of highly concentrated test solutions are normally required to control impurities at low levels. Under these conditions spike peaks were observed in the chromatograms of the test solutions making a proper evaluation of the impurity profile impossible. The influence of different eluent and ELSD parameters such as eluent composition, eluent flow-rate, ELSD scavenger gas flow-rate and evaporation temperature on the appearance of spike peaks was investigated. It could be shown that spike peaks can be avoided when selecting elevated eluent flow-rates and ESLD scavenger gas flow-rates. Moreover, eluents containing high amounts of organic modifier seem to foster the appearance of spike peaks. © 2010 Elsevier B.V. All rights reserved. Source


Almeling S.,European Directorate for the Quality of Medicines and Health Care | Ilko D.,University of Wurzburg | Holzgrabe U.,University of Wurzburg
Journal of Pharmaceutical and Biomedical Analysis | Year: 2012

Due to its wide field of application, sensitivity, wide range of linearity and the applicability to gradient elution, the most common detection technique for HPLC nowadays is UV/vis spectrophotometry. However, UV/vis detection comes to its limits when the analytes are lacking suitable chromophors or exhibit very different UV responses. In the past years, different types of evaporation/aerosol based HPLC detectors have been developed to fill this gap in HPLC detection. Amongst those, the corona-charged aerosol detector (CAD) is one of the most powerful and versatile representatives. In the recent past a variety of papers have been published, demonstrating the potential of the CAD in different fields of analytical chemistry. This paper is intended to provide an overview of the key performance characteristics and manifold applications for HPLC-CAD in the field of pharmaceutical analysis. © 2012 Elsevier B.V. Source


Holzgrabe U.,University of Wurzburg | Nap C.-J.,European Directorate for the Quality of Medicines and Health Care | Almeling S.,European Directorate for the Quality of Medicines and Health Care
Journal of Chromatography A | Year: 2010

In this study a reversed phase ion-pair high-performance liquid chromatography (HPLC) method using charged aerosol detection (CAD) was developed and fully validated for the pharmaceutical quality control of l-aspartic acid (Asp). With a slight modification, the method also allows the evaluation of related substances in l-alanine (Ala). The method enables simultaneous control of related amino acids and of possibly occurring organic acids contaminants. A minimum limit of quantification of 0.03% could be achieved for all occurring related substances. Moreover, the detector sensitivity of the CAD was compared with an evaporative light scattering detector (ELSD). Depending on the analyte the CAD was found to be 3.6-42 times more sensitive than the ELSD. The HPLC method was applied to the purity testing of 8 samples of pharmaceutical grade and reagent grade Asp and of 12 samples of Ala supplied by various manufacturers. Both substances were found to be of high purity (greater than 99.8% for Asp and greater than 99.9% for Ala). Malic acid and Ala were the major impurities in Asp. Asp and glutamic acid (Glu) were the only detectable impurities in Ala. © 2009 Elsevier B.V. All rights reserved. Source


Holzgrabe U.,University of Wurzburg | Nap C.-J.,European Directorate for the Quality of Medicines and Health Care | Beyer T.,University of Wurzburg | Almeling S.,European Directorate for the Quality of Medicines and Health Care
Journal of Separation Science | Year: 2010

The quality control of drugs is important for safety of patients and consumers. International pharmacopoeias mostly employed HPLC with UV detection for this purpose. This is always a problem when the drugs, such as most amino acids, are lacking a chromophor. Instead of UV detection, the impurity control of alanine was performed using charged aerosol detector, evaporative light-scattering detector, nano quantity analyte detector, MS detector, and as an orthogonal method, quantitative NMR spectroscopy. The charged aerosol detector, MS detector, and quantitative NMR spectroscopy provided similar and precise results, whereas the evaporative light-scattering detector and nano quantity analyte detector revealed some problems regarding sensitivity, linearity, and robustness. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA. Source


Holzgrabe U.,University of Wurzburg | Nap C.-J.,European Directorate for the Quality of Medicines and Health Care | Kunz N.,European Directorate for the Quality of Medicines and Health Care | Almeling S.,European Directorate for the Quality of Medicines and Health Care
Journal of Pharmaceutical and Biomedical Analysis | Year: 2011

For the control of impurities in streptomycin sulfate a reversed phase ion-pair high performance liquid chromatography (HPLC) method using charged aerosol detection (CAD) was developed. With this method, 21 impurities could be separated and tentatively identified using a combination of exact mass measurement by TOF-MS and MS/MS experiments with a triple quadrupole MS. For three impurities the suggested structures could be confirmed by in situ formation. The CAD detector response was found to be linear over 2 orders of magnitude allowing a straightforward quantification of all impurities. A limit of quantification of 0.09% for streptomycin sulfate and of 0.008% for streptidine sulfate (referred to the concentration of the 5. mg/ml test solution) could be achieved. The HPLC method was applied to the purity testing of 12 samples of commercially available streptomycin sulfate from different manufacturers. Impurity levels between 4.6% and 16.0% were found. The current European Pharmacopoeia monograph for streptomycin sulfate only limits streptomycin B by a TLC test to 3.0%. Therefore, the results of this study underline the importance of introducing a state-of-the-art test for the control of impurities in the monograph. The new HPLC-CAD method is considered suitable for this purpose. © 2011 Elsevier B.V. Source

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