Ionic liquids as superior solvents for headspace gas chromatography of residual solvents with very low vapor pressure, relevant for pharmaceutical final dosage forms.

1-n-Butyl-3-methylimidazolium dimethyl phosphate (BMIM DMP) was identified as the most suitable ionic liquid as solvent for the headspace gas chromatographic analysis of solvents with very low vapor pressure such as dimethylsulfoxide, N-methylpyrrolidone, sulfolane, tetralin, and ethylene glycol in a realistic matrix of commonly used excipients (carboxymethylcellulose, magnesium stearate, guar flour, and corn starch) in pharmaceutical products. Limits of quantification and limits of detection were in the low microgram per gram range. The detection of traces of sulfolane in a real sample of tablets containing the drug cefpodoxim proxetil demonstrated the applicability of the method.

[1]  A. Berthod,et al.  Ionic liquids in separation techniques. , 2008, Journal of chromatography. A.

[2]  Jing-fu Liu,et al.  Disposable ionic liquid coating for headspace solid-phase microextraction of benzene, toluene, ethylbenzene, and xylenes in paints followed by gas chromatography-flame ionization detection. , 2005, Journal of chromatography. A.

[3]  Robin D. Rogers,et al.  Dissolution of Cellose with Ionic Liquids , 2002 .

[4]  Ye Jiang,et al.  Room temperature ionic liquid as matrix medium for the determination of residual solvents in pharmaceuticals by static headspace gas chromatography. , 2007, Journal of chromatography. A.

[5]  H. Bart,et al.  Ternary Liquid−Liquid Equilibria for Systems Containing Alcohol or Acetic Acid + Ester + 1-Ethyl-3-methylimidazolium Hydrogen Sulfate at 313.2 K Using Headspace Gas Chromatography , 2009 .

[6]  N. Novoselov,et al.  Ionic liquids as new solvents of natural polymers , 2008 .

[7]  F. Zhao,et al.  Ionic liquid-based headspace single-drop microextraction coupled to gas chromatography for the determination of chlorobenzene derivatives , 2009 .

[8]  Peter Wasserscheid,et al.  Ionic Liquids in Synthesis , 2002 .

[9]  F. Zhao,et al.  Coupling of ionic liquid-based headspace single-drop microextraction with GC for sensitive detection of phenols. , 2008, Journal of separation science.

[10]  D. Armstrong,et al.  Ionic liquids in separations. , 2007, Accounts of chemical research.

[11]  Jun Zhang,et al.  1-Allyl-3-methylimidazolium chloride room temperature ionic liquid: A new and powerful nonderivatizing solvent for cellulose , 2005 .

[12]  M. Valcárcel,et al.  Ionic liquid-based single-drop microextraction/gas chromatographic/mass spectrometric determination of benzene, toluene, ethylbenzene and xylene isomers in waters. , 2008, Journal of chromatography. A.

[13]  Anne S. Meyer,et al.  Predictions of flavonoid solubility in ionic liquids by COSMO-RS: experimental verification, structural elucidation, and solvation characterization , 2007 .

[14]  Hiroyuki Ohno,et al.  Cellulose dissolution with polar ionic liquids under mild conditions: required factors for anions , 2008 .

[15]  S. Ashcroft,et al.  Isothermal vapor-liquid equilibriums for the systems toluene-n-heptane, toluene-propan-2-ol, toluene-sulfolane, and propan-2-ol-sulfolane , 1979 .

[16]  V. Pino,et al.  Examination of analyte partitioning to monocationic and dicationic imidazolium-based ionic liquid aggregates using solid-phase microextraction-gas chromatography. , 2007, Journal of chromatography. A.

[17]  K. Urakami,et al.  Matrix media selection for the determination of residual solvents in pharmaceuticals by static headspace gas chromatography. , 2004, Journal of chromatography. A.

[18]  H. Cortes,et al.  Background vapor from six ionic liquids and the partition coefficients and limits of detection for 10 different analytes in those ionic liquids measured using headspace gas chromatography. , 2008, Journal of chromatography. A.

[19]  M. Valcárcel,et al.  Direct coupling of ionic liquid based single-drop microextraction and GC/MS. , 2008, Analytical chemistry.

[20]  F. Marken,et al.  An ionic liquid as a solvent for headspace single drop microextraction of chlorobenzenes from water samples. , 2007, Analytica chimica acta.

[21]  Chao Tai,et al.  Ionic liquid for high temperature headspace liquid-phase microextraction of chlorinated anilines in environmental water samples. , 2005, Journal of chromatography. A.

[22]  M. Andre,et al.  Ionic liquids as advantageous solvents for headspace gas chromatography of compounds with low vapor pressure. , 2005, Analytical chemistry.

[23]  L. Vidal,et al.  Simple and commercial readily-available approach for the direct use of ionic liquid-based single-drop microextraction prior to gas chromatography determination of chlorobenzenes in real water samples as model analytical application. , 2009, Journal of chromatography. A.

[24]  C. Poole,et al.  Comparison of elelctron-capturing boronic acids for the selective analysis of bifunctional compounds , 1979 .

[25]  Jing-fu Liu,et al.  Ionic liquids in sample preparation , 2009, Analytical and bioanalytical chemistry.

[26]  G. Carrera,et al.  Static headspace gas chromatographic method for quantitative determination of residual solvents in pharmaceutical drug substances according to european pharmacopoeia requirements. , 2004, Journal of chromatography. A.

[27]  T. Douglas Vapor Pressure of Methyl Sulfoxide from 20 to 50°. Calculation of the Heat of Vaporization , 1948 .

[28]  S. Verevkin Determination of vapor pressures and enthalpies of vaporization of 1,2-alkanediols , 2004 .

[29]  I. Mokbel,et al.  Description of vapour–liquid and vapour–solid equilibria for a group of polycondensed compounds of petroleum interest , 1998 .

[30]  S. Himmler,et al.  Imidazolium dialkylphosphates—a class of versatile, halogen-free and hydrolytically stable ionic liquids , 2007 .

[31]  M. Valcárcel,et al.  Determination of trihalomethanes in waters by ionic liquid-based single drop microextraction/gas chromatographic/mass spectrometry. , 2008, Journal of chromatography. A.

[32]  Ying Liu,et al.  Establishment of a knowledge base for identification of residual solvents in pharmaceuticals. , 2006, Analytica chimica acta.

[33]  M. Rocheleau,et al.  Measuring residual solvents in pharmaceutical samples using fast gas chromatography techniques. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[34]  J. Vial,et al.  Use of solid-phase microextraction coupled with gas chromatography for the determination of residual solvents in pharmaceutical products. , 2003, Journal of chromatography. A.

[35]  Y. Liu,et al.  Preliminary identification and quantification of residual solvents in pharmaceuticals using the parallel dual-column system. , 2007, Journal of chromatography. A.