Simultaneous multiplexed quantification of nicotine and its metabolites using surface enhanced Raman scattering

Area of Science:

• Analytical Chemistry
• Spectroscopy
• Chemometrics

Background:

• Accurate detection of xenobiotics and metabolites is crucial for drug dosing, therapy, and substance abuse monitoring.
• Raman spectroscopy provides molecular specificity, and surface-enhanced Raman scattering (SERS) significantly amplifies this signal.
• Simultaneous analysis of multiple compounds, including drugs and their metabolites, often requires complex separation techniques.

Purpose of the Study:

• To develop and validate a novel method using SERS combined with chemometrics for the simultaneous quantification of nicotine and its major metabolites, cotinine and trans-3′-hydroxycotinine.
• To optimize SERS conditions for enhanced signal detection of these analytes.
• To demonstrate the feasibility of SERS as a rapid analytical tool for xenobiotic analysis.

Main Methods:

• Surface-enhanced Raman scattering (SERS) was employed for spectral acquisition.
• Optimization of SERS conditions, including pH, was performed for individual analytes (nicotine, cotinine, trans-3′-hydroxycotinine).
• Chemometric models, specifically kernel-partial least squares (K-PLS) and artificial neural networks (ANNs), were developed and validated using bootstrap resampling for quantitative analysis.

Main Results:

• SERS signals were maximized at different pH values for each analyte: pH 3 for nicotine, pH 10 for cotinine, and pH 11 for trans-3′-hydroxycotinine.
• Simultaneous analysis of ternary mixtures (nicotine, cotinine, trans-3′-hydroxycotinine) in the concentration range of 10⁻⁷–10⁻⁵ M was achieved.
• Chemometric models accurately quantified all three analytes, with root mean squared error of prediction between 5–9%.

Conclusions:

• SERS combined with chemometrics provides a powerful and rapid approach for the simultaneous analysis of multiple xenobiotics and their metabolites.
• This method eliminates the need for lengthy chromatographic separations, offering a significant advantage in analytical workflows.
• The developed technique is demonstrated for the xenobiotic nicotine and its two major xenometabolites, showing high accuracy and potential for clinical and forensic applications.