title: Identification and control of impurities in streptomycin sulfate by high-performance liquid chromatography coupled with mass detection and corona charged-aerosol detection.
abstract: 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 5mg/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.
authors.affiliation: University of Wuerzburg, Institute of Pharmacy and Food Chemistry, Am Hubland, 97074 Wuerzburg, Germany. u.holzgrabe@pharmazie.uni-wuerzburg.de
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
authors.forename: Cees-Jan
authors.initials: CJ
authors.lastname: Nap
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kunz
authors.forename: Stefan
authors.initials: S
authors.lastname: Almeling
mesh_terms: D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000592:standards; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D004340:Drug Contamination / Q000517:prevention & control*; D017408:Guidelines as Topic; D015394:Molecular Structure; D011786:Quality Control; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013307:Streptomycin / Q000032:analysis* / Q000592:standards; D053719:Tandem Mass Spectrometry; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D013307:Streptomycin