Aerogel Pore-Confined High-Loading MOF-199 for Micro-Solid-Phase Extraction of Methorphan Enantiomer in Biological Samples

Dextromethorphan is a widely used clinical antitussive, while its enantiomer, levomethorphan, is a controlled substance. Chiral separation and trace detection of the two enantiomers in biological samples are critically important. Herein, a micro-solid-phase extraction method coupled with enantioselective ultra-high performance liquid chromatography–mass spectrometry (UHPLC–MS) was proposed for the analysis of methorphan enantiomers. MOF-199/cellulose aerogel spheres fabricated via a facile in situ growth strategy were employed as the sorbent. By immersing Cu 2+ -rich cellulose aerogel in H 3 BTC (1,3,5-benzene tricarboxylate) solutions at varied concentrations, MOF-199/cellulose aerogels with tunable MOF-199 loadings (28.8%, 38.1%, 43.8%) were fabricated. Characterization results verified that MOF-199 was uniformly anchored in the pore channels of cellulose aerogel, which not only enhanced its specific surface area from 33.9 to 143.6 m 2 /g, but also mitigated the aggregation and poor recyclability of powdered MOF-199. The electrostatic attraction, chelation, and hydrogen-bonding interactions accounted for the effective extraction for dextro- and levo-methorphan. Under optimized conditions, this method exhibited favorable linearity in the range of 0.02–10.0 µg/L, with intra- and inter-day precisions of 4.9%–5.0% and 7.7%–9.7%, respectively. The limits of detection were 0.01–0.02 µg/L, respectively. Recoveries of dextro- and levo-methorphan from urine and hair samples were in the ranges of 88.9%–119.3% and 78.6%–115.7%, respectively. This method provides an effective strategy for the determination of methorphan enantiomers in biological samples, featuring rapid pretreatment, low organic solvent consumption, as well as facile operation.