title: Liquid paraffin as new dilution medium for the analysis of high boiling point residual solvents with static headspace-gas chromatography.
abstract: Residual solvents are volatile organic compounds which can be present in pharmaceutical substances. A generic static headspace-gas chromatography analysis method for the identification and control of residual solvents is described in the European Pharmacopoeia. Although this method is proved to be suitable for the majority of samples and residual solvents, the method may lack sensitivity for high boiling point residual solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide and benzyl alcohol. In this study, liquid paraffin was investigated as new dilution medium for the analysis of these residual solvents. The headspace-gas chromatography method was developed and optimized taking the official Pharmacopoeia method as a starting point. The optimized method was validated according to ICH criteria. It was found that the detection limits were below 1μg/vial for each compound, indicating a drastically increased sensitivity compared to the Pharmacopoeia method, which failed to detect the compounds at their respective limit concentrations. Linearity was evaluated based on the R(2) values, which were above 0.997 for all compounds, and inspection of residual plots. Instrument and method precision were examined by calculating the relative standard deviations (RSD) of repeated analyses within the linearity and accuracy experiments, respectively. It was found that all RSD values were below 10%. Accuracy was checked by a recovery experiment at three different levels. Mean recovery values were all in the range 95-105%. Finally, the optimized method was applied to residual DMSO analysis in four different Kollicoat(®) sample batches.
authors.affiliation: Laboratory for Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, O & N 2, Herestraat 49 (PB 923), B-3000 Leuven, Belgium.
authors.forename: Ward
authors.initials: W
authors.lastname: D'Autry
authors.forename: Chao
authors.initials: C
authors.lastname: Zheng
authors.forename: John
authors.initials: J
authors.lastname: Bugalama
authors.forename: Kris
authors.initials: K
authors.lastname: Wolfs
authors.forename: Jos
authors.initials: J
authors.lastname: Hoogmartens
authors.forename: Erwin
authors.initials: E
authors.lastname: Adams
authors.forename: Bochu
authors.initials: B
authors.lastname: Wang
authors.forename: Ann
authors.initials: A
authors.lastname: Van Schepdael
mesh_terms: D002623:Chemistry Techniques, Analytical / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002849:Chromatography, Gas / Q000295:instrumentation / Q000379:methods*; D008899:Mineral Oil / Q000737:chemistry*; D009930:Organic Chemicals / Q000032:analysis; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D014835:Volatilization
chemical_list: D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; D012997:Solvents; D008899:Mineral Oil