Systematic investigation of analyte protectants to overcome matrix effects for gas chromatographic analysis of tobacco alkaloids and primary aromatic amines across diverse matrices

The application of analyte protectants (APs) is recognized as an effective and practical strategy to enhance analyte signals in matrix-free solutions and compensate for matrix effects (MEs) in gas chromatography (GC) analysis. However, systematic investigations into promising APs for basic analytes and elucidation of the underlying molecular mechanisms remain limited. In this study, two classes of basic analytes with diverse polarity and basicity, including tobacco alkaloids (TAs) and primary aromatic amines (PAAs), were selected as target analytes. A total of 29 candidates covering a broad range of polarity, basicity, and volatility were systematically evaluated to identify the promising APs for TAs and PAAs. According to individual and average analyte peak enhancement factors, several polyamines, including diethylenetriamine, tris(2-aminoethyl)amine, spermine, pentaethylenehexamine, and the diamine 1,11-diaminoundecane, were identified as the potential APs. Corresponding combinations of these APs for TAs and PAAs at optimized concentrations were validated to significantly reduce the limits of quantification from 1.58–307.85 to 1.26–43.43 ng/mL in solvent and improve recovery rates from 92.3–352.1 to 80.3–111.5% in complex matrices. Consistent signal responses across diverse matrices further highlight the developed APs effectively overcome the MEs, ensuring the accurate and robust determinations in practical applications. Furthermore, density functional theory (DFT) calculations revealed that the superior enhancement effects of these APs are primarily attributed to lower interaction energies and stronger hydrogen-bonding interactions with silanol groups in the GC system.