| Title: | Liquid paraffin as new dilution medium for the analysis of high boiling point residual solvents with static headspace-gas chromatography |
| Author(s): | D'Autry W; Zheng C; Bugalama J; Wolfs K; Hoogmartens J; Adams E; Wang B; Van Schepdael A; |
| Address: | "Laboratory for Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, O & N 2, Herestraat 49 (PB 923), B-3000 Leuven, Belgium" |
| DOI: | 10.1016/j.jpba.2011.04.004 |
| ISSN/ISBN: | 1873-264X (Electronic) 0731-7085 (Linking) |
| 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 1mug/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((R)) sample batches" |
| Keywords: | "Chemistry Techniques, Analytical/methods Chemistry, Pharmaceutical/methods Chromatography, Gas/instrumentation/*methods Mineral Oil/*chemistry Organic Chemicals/analysis Pharmaceutical Preparations/analysis/chemistry Reproducibility of Results Solvents/ch;" |
| Notes: | "MedlineD'Autry, Ward Zheng, Chao Bugalama, John Wolfs, Kris Hoogmartens, Jos Adams, Erwin Wang, Bochu Van Schepdael, Ann eng England 2011/05/10 J Pharm Biomed Anal. 2011 Jul 15; 55(5):1017-23. doi: 10.1016/j.jpba.2011.04.004. Epub 2011 Apr 12" |
