Robust graphene oxide composite aerogel for micro solid-phase extraction of methorphan enantiomers from biological matrices.

Methorphan exists as two optically active enantiomers, levomethorphan (LVM) and dextromethorphan (DXM). DXM is a widely utilized central antitussive, whereas LVM is a strictly regulated controlled substance. This study established a method combining micro-solid-phase extraction with enantioselective high-performance liquid chromatography-mass spectrometry (LC-MS) for the simultaneous determination of LVM and DXM in human urine and nail samples. A spherical porous graphene oxide composite aerogel (GO@CNF/CMC) served as the extraction sorbent. It was synthesized by covalently crosslinking graphene oxide (GO), cellulose nanofibers (CNF), and carboxymethyl chitosan (CMC) via a combined sol-gel and dropwise addition strategy. Aerogels with various GO mass fractions were fabricated for sorption optimization. With a maximum GO loading of 11.2 wt%, the aerogel delivered superior extraction efficiency owing to its large specific surface area and synergistic intermolecular interactions including hydrogen bonding, π-π stacking and electrostatic attraction. The aerogel exhibited excellent mechanical stability and recyclability, with nearly consistent extraction efficiency over 15 extraction cycles. Under optimized extraction conditions, the method exhibited good linearity in the range of 0.05-10 μg/L. The limits of detection were 0.01 μg/L for both LVM and DXM. The spiked recoveries in urine and nail samples ranged from 81.6% to 108.4%, and matrix effects ranged from 83.3% to 105.7%. This method provides a facile, rapid, green and sensitive analytical strategy for the trace analysis of methorphan enantiomers in complex biological matrices.