title: Evaluation of the European Pharmacopoeia method for control of residual solvents in some antibiotics.
abstract: Residual solvents (RS) are volatile organic chemicals that are used or produced during the manufacturing process of drug substances or excipients. The European Pharmacopoeia (Ph. Eur.) limits the amount of RS in pharmaceuticals, considering the International Conference on Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines for RS. According to the Ph. Eur. general method, water insoluble samples may be analyzed using DMF as dilution solvent at high equilibration temperatures such as 105 degrees C. This could be problematic in the case of antibiotics, many of which are water insoluble and temperature sensitive. Moreover, antibiotics are complex in nature and beside RS, one can expect several other volatile impurity peaks in the chromatogram. In this study, the Ph. Eur. method for RS analysis was evaluated for selected groups of antibiotics. An alternative dilution medium was proposed (DMSO-water), which offers optimum sensitivity while working at lower equilibration temperatures such as 80 degrees C. The optimized method was investigated for precision, accuracy, linearity and detection limits.
authors.affiliation: Laboratory for Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, K.U.Leuven, Leuven, Belgium.
authors.forename: Yarramraju
authors.initials: Y
authors.lastname: Sitaramaraju
authors.forename: Adil
authors.initials: A
authors.lastname: Riadi
authors.forename: Ward
authors.initials: W
authors.lastname: D'Autry
authors.forename: Kris
authors.initials: K
authors.lastname: Wolfs
authors.forename: Jos
authors.initials: J
authors.lastname: Hoogmartens
authors.forename: Ann
authors.initials: A
authors.lastname: Van Schepdael
authors.forename: Erwin
authors.initials: E
authors.lastname: Adams
mesh_terms: D000081:Acetamides / Q000032:analysis; D000900:Anti-Bacterial Agents / Q000032:analysis*; D004121:Dimethyl Sulfoxide / Q000032:analysis; D004126:Dimethylformamide / Q000032:analysis; D004340:Drug Contamination / Q000517:prevention & control*; D004583:Electrons; D005060:Europe; D005079:Excipients / Q000737:chemistry; D017408:Guidelines as Topic; D006801:Humans; D007093:Imidazoles / Q000032:analysis; D048289:Imidazolidines / Q000032:analysis / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D009930:Organic Chemicals / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000032:analysis*; D014835:Volatilization
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D005079:Excipients; D007093:Imidazoles; D048289:Imidazolidines; D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; D012997:Solvents; D004126:Dimethylformamide; C013959:dimethylacetamide; D004121:Dimethyl Sulfoxide