Comprehensive classification of methylation mechanisms and their integration with microextraction techniques for gas chromatographic analysis

This review focuses on derivatization strategies used in methylation and their integration with microextraction techniques (METs) to improve detectability and/or ease of quantification in gas chromatography (GC) analysis. Methylation is the preferred derivatization technique in GC primarily because it replaces polar, active hydrogen atoms with non-polar methyl groups, it slightly increases the molecular mass, is readily found in mass spectral libraries, and offers a wide variety of possibilities for interaction with the molecule. This structural modification significantly enhances analyte volatility and thermal stability while minimizing peak tailing caused by secondary interactions with the stationary phase. Consequently, it enables the efficient, high-resolution separation of otherwise non-volatile or thermally labile compounds. Since Knapp's 1979 publication, there have been several key additions to the range of derivatization reagents related to methylation, frequently involving the use of diazomethane. Indeed, numerous new specialized reagents have been introduced, such as new methods for chiral differentiation and quantification, as well as significant improvements in various derivatization procedures, thanks in part to the use of robotics. To date, significant improvements and a reduction in analyte isolation times have been achieved, resulting in a reduction in overall preparation times, thanks in part to the introduction of METs on solid sorbent. This review focuses on the evolution of METs over the last decade, on examples of recent development in METs that, in the authors' opinion, offer advantages or advances in terms of sample preparation time or detection sensitivity. Therefore, methods in which derivatization and extraction are performed simultaneously, or derivatization is coupled with sample introduction into the GC are highlighted.