33


area were satisfied for all analytes when DMAC was used as headspace solvent (Table


3). For the ionic liquid [BMIM][BF4], dichloromethane (%RSD = 88.53), acetonitrile (%RSD = 100.08), and n-butyl acetate (%RSD = 16.7) do not satisfy the method requirements. This is due to the interfering peak in the solvent which prevents quantification of these residual solvents.


The validation criteria for %RSD retention time (not shown) was satisfied for all analytes with the exception of dichloromethane in the ionic


liquid [BMIM][BF4] (%RSD = 1.36). This has been explained due to a significant amount of this residual solvent in the ionic liquid itself, which leads to inconsistent results.


Conclusion


The performance of ionic liquids for headspace GC solvents was assessed and has provided invaluable insight into the enhancement of sensitivity towards residual solvents.


In all cases, ionic liquids increased the response towards the residual solvents in comparison to DMAC. The relative response of the analytes in the ionic solvents was partially explained by a combination linear free energy models, however, some trends were not fully accounted for.


Significant volatile organic impurities were


present in [BMIM][PF6] and therefore this ionic liquid was shown to be unsuitable for the determination of acetone and


dichloromethane. [BMIM][BF4] had a large endogenous interfering peak which co-eluted with the acetonitrile, dichloromethane and acetone peaks making the determination of these solvents impossible.


In conclusion, ionic liquids have shown promise as solvents in static headspace Gas Chromatography for low boiling point residual solvent analysis. The enhancement of headspace sensitivity by ionic liquids could be further exploited to achieve low limits of quantification for residual solvents and the potential to use smaller quantities of the active pharmaceutical ingredient.


Acknowledgements


The Author would like to thank her supervisor, E. W. Hammersley for all his patient supervision and tuition in the technique of Gas Chromatography. I am truly grateful to Research Analytics, Pfizer Global Research and Development, Sandwich, for all their support throughout my industrial placement year.


i Armstrong, D.W.; Zhang, L-K; He, L; Gross,


Anastas, P. Zimmerman, J.B., Environ. Sci. Technol. 2003, 37, 94A


M. L. Anal.Chem., 2001, 73 3679. ii


iii Weyershausen B; Lehman B. Green


Chem.,2005, 7, 15. iv


Berthod, A; He, L.; Armstrong, D.W.;


Chromatographia, 2001, 53, 63 v


Wasser P., Welton, T. (Edds.) Ionic Liquids


in Synthesis, Wiley-VCH, Weinheim, 2003 vi


Carmichael A., J.; Seddon, K.R. J Phys


Org. Chem 2000, 13, 591 vii


Harmonised Tripartite Guideline on Impurities: Residual Solvents (Q3C), International conference on Harmonisation of Technical Requirements for Registrations of Pharmaceuticals for Human Use (ICH),


124, 14247 viii


Geneva, 1997 ix


Liu, F.-H.; Jiang, Y., J. Chromatogr. A.


2007, 1167, 116 x


Abraham, M.H.;Whiting, G.S; Doherty, R.M.; Sheuly, W. J. J. Chromatgr. 1990, 518, 329


Anderson, J. L.; J. Am. Chem. Soc. 2002,


Components Methanol


n-pentane ethanol


diethyl ether acetone


propan-2-ol acetonitrite


dichloromethane t-butanol


n-propanol


ethyl acetate chloroform cyclohexane 1, 4-dioxan


4-methyl-2-pentanone toluene


n-butyl acetate


DMAC 1.59


0.86 2.45 0.65 0.46 8.57 1.94 1.21 0.76 1.19 1.06 0.85 6.46 1.56 2.31 4.18 2.67


[BMIM][BF4] 2.68 6.05 4.1


4.07 1.33 3.52


100.08 88.53 5.4


3.11 2.52 4.88 2.13 2.76 3.43 3.35 16.7


[BMIM][PF6] 5.49 6.23 4.21 6.6


0.82 6.98 5.94 0.78 7.32 5.59 6.23 7.54 7.89 6.84 6.25 5.14 5.92


Table 3: Results to show the reproducibility of the different headspace solvents determined by %RSD peak area.


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