title: Static headspace gas chromatographic method for quantitative determination of residual solvents in pharmaceutical drug substances according to european pharmacopoeia requirements.
abstract: A static headspace (HS) gas chromatographic method for quantitative determination of residual solvents in a drug substance has been developed according to European Pharmacopoeia general procedure. A water-dimethylformamide mixture is proposed as sample solvent to obtain good sensitivity and recovery. The standard addition technique with internal standard quantitation was used for ethanol, tetrahydrofuran and toluene determination. Validation was performed within the requirements of ICH validation guidelines Q2A and Q2B. Selectivity was tested for 36 solvents, and system suitability requirements described in the European Pharmacopoeia were checked. Limits of detection and quantitation, precision, linearity, accuracy, intermediate precision and robustness were determined, and excellent results were obtained.
authors.affiliation: Analysis R&D Department, Research Centre Sant Feliu de Llobregat, Almirall, Laureano Miró 408-410, 08980 Sant Feliu de Llobregat, Barcelona, Spain. rotero@almirall.es
authors.forename: Raquel
authors.initials: R
authors.lastname: Otero
authors.forename: Guillem
authors.initials: G
authors.lastname: Carrera
authors.forename: Joan Francesc
authors.initials: JF
authors.lastname: Dulsat
authors.forename: José Luís
authors.initials: JL
authors.lastname: Fábregas
authors.forename: Juan
authors.initials: J
authors.lastname: Claramunt
mesh_terms: D002849:Chromatography, Gas / Q000379:methods*; D017408:Guidelines as Topic; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012997:Solvents / Q000032:analysis*
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents